Diabetic Neuropathy Alcohol Use

Dr. Jason Lawrence Meyer is a chiropractor who runs the World of Wellness Chiropractic Offices in Fort Worth and Arlington, TX. wowhealthcenters Integrative medicine which is also called integrated medicine or integrative health, combines alternative medicine with evidencebased medicine. Proponents claim that it treats the whole person , focuses on wellness and health rather than on treating disease, and emphasizes the patientphysician relationship. The Defining Principles of Integrative Medicine 1. Patient and practitioner are partners in the healing process. 2. All factors that influence health, wellness, and disease are taken into consideration,.

Including mind, spirit, and community, as well as the body. 3. Appropriate use of both conventional and alternative methods facilitates the body’s innate healing response. 4. Effective interventions that are natural and less invasive should be used whenever possible. 5. Integrative medicine neither rejects conventional medicine nor accepts alternative therapies uncritically. 6. Good medicine is based in good science. It is inquirydriven and open to new paradigms. 7. Alongside the concept of treatment, the broader concepts of health promotion and the prevention of illness are paramount. 8. Practitioners of integrative medicine should exemplify its principles and commit themselves.

To selfexploration and selfdevelopment. World of wellness is a group of medical offices specializing in functional medicine, natural wellness and prevention. We offer integrated services providing fabulous bodywork in a fun and upbeat environment. our highly trained staff including Dr. Jason Meyer DC offer services such as natural medicine, pain relief, rehabilitation, therapy, massage, weightloss, nutrition, allergy testing, allergy management, arthritis relief, pain management, headache relief, and more, our mission statement and corporate purpose is to help people in the country become happier and healthier through natural healthcare. We are fully staffed with medical doctors,.

Nurse practitioners, chiropractors such as Dr. Jason Lawrence Meyer and licensed massage therapists and we are dedicated to help you obtain optimum wellness. Have you explored the World of wellness Fort Worth functional medicine World of Wellness would like to show you how optimizing your health and wellness can, in turn, eliminate any chronic pain that you may suffer from. Dr. Jason Meyer and Our team invites you to pay us a visit at our Fort Worth natural wellness clinic, where you will receive focused attention from a whole team of medical professionals.

We pride ourselves in working closely with each patient, explaining to them the potential sources of their pain and how that pain can be eliminated. World of Wellness provides Fort Worth and Arlington wellness and prevention that helps hold off chronic pain. Through our allnatural methods, we are able to treat a wide variety of ailments, including, but certainly not limited to Low back pain Migraine headaches Sciatica Neuropathy Neck pain Sports injuries Allergies Weight loss What makes our Fort Worth Chiropractic and functional medicine so effective is that we use natural methods of treatment instead of introducing harsh chemicals or subjecting.

The body to painful surgical procedures. Prescription medication might take away your pain, but not without a price. Many of these powerful medications can cause damage to other parts of your body. This is why our wellness clinic in Fort Worth shies away from using these drugs. The experienced staff at our functional medicine clinic in Fort Worth TX is truly unique. We staff a whole team of medical professionals who specialize in various areas of health and wellness. This means all of our resources are together under one roof. Many traditional.

Doctors will refer patients to other specialists because they are not equipped to handle certain treatments. Keeping our patients in one facility ensures strong communication and lets you garner the advantages of working with an entire team of professionals rather than just one doctor. We want to meet with you and open your eyes to a new way of reducing or eliminating your chronic pain. World of Wellness offers free consultation appointments. Make an appointment now and see what our Fort Worth functional medicine methods can do for you. Dr. Jason Meyer D.C. Jason Meyer Chiropractor.

Peripheral Neuropathy Numb Feet and Hands Symptoms Resolved TheVillagesNeuropathy

When you had originally presented to the office, you presented with chronic numbness, tingling, burning, in the hands and the feet. It limited your ability to walk, limited your ability to sleep, your ability to relax. We’ve completed a course of treatment here with the Davis neuropathy program, how have you done with the treatment and how are you feeling today I feel wonderful. I have to tell you that the treatment, I was on both programs. Before I came in, all that I knew that I had was peripheral neuropathy after your exam, after.

You examined me. We found out that I had also spinal stenosis in my spine. I have followed your program, both of your programs, the DRS program and the peripheral neuropathy program, and I am doing beautifully. I can now walk without assistance which I was having to hold my husband’s hand or somebody’s hand when I was shopping or doing anything. I could not drive by myself. I feel like a whole person now. Well congratulations on your results and we’re very proud to have you here as a patient. What else would you like to have.

Peripheral Neuropathy Symptoms Relieved DavisClinic

When you originally presented to the office you presented with very very intense peripheral neuropathy pain in the lower legs and feet. How have you been responding to our peripheral neuropathy treatments, and how do you feel today Today I feel real good, when I first started i couldn’t feel a thing under the bottom of my feet. I couldn’t feel the carpet, now I can walk on my carpet at home and if there are any crumbs I can feel those and find them. Before I couldn’t feel them. As far as my legs go I had it felt like there.

Heavy Drinking Declines Memory In Men Study

This week, you’ve heard a little caffeine can boost your memory and now, a new study suggests heavy alcohol use might result in a decline in memory, at least in men. London researchers studied more than 5,000 men and 2,000 women in the U.K. and found a significant decline in memory and mental functions in men who drank more than 36 grams of alcohol a day about two and a half drinks. Via USA Today, ABC Every few years since 1997, the study participants took memory and reasoning tests, such as writing.

Down as many words beginning with the letter s as they could in a minute or solving mathematical word problems. Via NBC, News 12 The study confirms past research indicating a little alcohol is probably not going to affect you, but heavy consumption is likely harming cognitive power similar to premature aging. Via Neurology According to the study’s lead author, the men who drank more than twoandahalf drinks per day experienced accelerated memory decline of up to 6 years. Via WJBK It’s important to note that alcohol consumption was selfreported in the study, meaning some.

People might have underestimated how much they actually drink. Also, the study defined alcoholic beverages as measures of spirits, glasses of wine and pints of beer which are arbitrary. In the U.S. the National Institute on Alcohol Abuse and Alcoholism defines one drink as a regular can of beer, 5 ounces of wine or a shot of hard liquor. And although the study included women, the researchers found no clear results for them and suggest further studies are needed to determine whether these findings are true regardless of gender. Via Neurology.

Peripehral Neuropathy Painful Legs and Feet Pain Reduced DavisSpineInstitute

When you originally presented to the office you presented very very intense peripheral neuropathy pain over your knee, lower legs, and feet. We’ve been managing you here for a good six weeks on the peripheral neuropathy based program. How have you been responding to the program, and what’s been your experiences today When I first started it took a while before I was able to say that and feel an improvement in my problem. Particularly on the bottom of my feet, the sensory part. I could feel the difference between tile and.

Wood floor, the coldness of each and the carpet. Before I started the program I hardly could feel the difference between those items. The discoloration of the neuropathy on my legs is a great improvement and I’m very pleased with that. It does not, particularly on my right leg, it does not weep water anymore, the skin does not break, and that is a great improvement as far as I’m concerned. On my knees there is some swelling going on on my right knee, there is improvement on the inside of my knee. The outside is still a little.

Genomic Factors Impacting Health in Peoples of African Descent

Gtgt GOOD AFTERNOON, EVERYONE. I’M FRANCIS COLLINS, IT’S MY PLEASURE TO WELCOME TO YOU FIRST WEDNESDAY AFTERNOON LECTURE OF 2013. WITH MANY MORE TO COME ON SUBSEQUENT WEDNESDAY AFTERNOONS AND APPRECIATE EVERYBODY WHO IS ABLE TO GATHER HERE IN THE AUDITORIUM AND ALL THOSE MANY WHO ARE WATCHING ON THE WEB, BECAUSE WE TRY TO MAKE THIS AS ACCESSIBLE AS POSSIBLE TO BUSY PEOPLE ALL AROUND THIS CAMPUS AND IN OTHER PLACES. WE VERY FORTUNATE TODAY TO HAVE AS OUR PRESENTER, Dr. BARRY FREEDMAN, WHO IS PROFESSOR OF INTERNAL MEDICINE AND CHIEF OF.

THE SECTION OF NEPHROLOGY AT THE WAKE FOREST SCHOOL OF MEDICINE IN WINSTON, SALEM, NORTH CAROLINA. HE HAS AN INTERESTING HISTORY IN TERMS OF HIS TRAINING, WHICH MAY PLAIN WHY DESPITE HAVING LIVED SOUTH OF THE MASON DIXON LINE FOR NEARLY 30 YEARS, YOU WON’T DETECT MUCH IN TERMS OF A PERFECTION OF THE SOUTHERN ACCENT. BARRY WAS BORN IN NEW YORK CITY, ATTENDED BROOKLYN COLLEGE, GRADUATED SUMA CUM LAUDE AND DID HIS MEDICAL TRAINING AT SUNNI DOWN STATE COLLEGE OF MEDICINE BEFORE DEPARTING FOR VIRGINIA AND THEN NORTH CAROLINA. AND SINCE ARRIVING IN WAKE.

FOREST FOR A NEPHROLOGY FELLOWSHIP, HE HAS RISEN THROUGH THE RANKS AND BECAME NEPHROLOGY CHIEF IN 2000. HE HAS BEEN A PROLIFIC INVESTIGATOR, AUTHORED OVER 350 PAPERS AND BOOK CHAPTERS. HIS WORK HAS BEEN CONTINUOUSLY FUNDED BY NIH GRANTS FROM SEVERALINS INSTITUTIONS NIDDK, NHLBI, AND CURRENTLY THE PI ON FOUR NIH GRANTS ASSOCIATE INVESTIGATOR ON EIGHT OTHERS. SO HE HAS A STRONG WORK ETHIC. HIS RESEARCH HAS FOCUSED SPECIFICALLY ON GENETICS SUSCEPTIBILITY TOW TYPE II DIABETES AS WELL AS KIDNEY, CARDIOVASCULAR AND BONE DISEASES WITH EMPHASIS ON THE AFRICAN AMERICAN POPULATION.

ONE OF HIS CONTRIBUTIONS, WHICH I THINK HE WILL TALK ABOUT LATER IN THE PRESENTATION, IS THE ROLE OF THE PROTEIN L1 GENE A VARIANT IN THAT GENE IN TERMS OF PREDISPOSITION TO KIDNEY DISEASE BUT ALSO PROVIDING PROTECTION AGAINST A PARTICULAR INFECTIOUS DISEASE NAMELY AFRICAN SLEEPING SICKNESS. THIS HAS BEEN ONE OF THE MOST EXCITING STORIES TO COME OUT OF THIS INTERFACE BETWEEN ENVIRONMENTAL INFLUENCES AND GENETIC VARIATION SINCE THE ORIGINAL DESCRIPTION OF SICKLE CELL AND THE PROTECTION AGAINST MALARIA AND THE HETEROZYGOTE. SO I THINK WE ARE IN FOR A VERY.

INTERESTING PRESENTATION WITH A FOCUS ON HEALTH DISPARITIES, A TOPIC OF ERK ENORMOUS IMPORTANCE FOR ALL OF US. SO JOIN ME IN WELCOMING Dr. BARRY FREEDMAN. APPLAUSE Y. gtgt THANK YOU Dr. COLLINS, Dr. ROGERS, AND ALL MY GRIT FRIENDS AT NIH INTRAMURAL AND EXTRAMURAL. IT’S A TREMENDOUS HONOR TO GO HERE AND I’M GLAD YOU WARNED BENCH MY FASTTALKING NEW YORK ACCENT. I’M GOING TO TALK ABOUT A TOPIC THAT IS STRIKINGLY CONTROVERSIAL TO EVERYONE IN THE GENERAL POPULATION, BUT HAS NEVER BEEN TO ME. AND IT’S THE CONCEPT THAT THERE.

ARE DIFFERENTIAL DISTRIBUTION OF RISK VARIETIES IN CERTAIN POPULATION GROUPS THAT PUT THEM AT UNIQUE SUSCEPTIBILITY OR PROTECTION FROM COMPLEX DISEASE. AND IT’S STRIKING TO ME HOW MANY PEOPLE FIND THAT CONCEPT THREATENING OR CANOTING BIAS, AND I THINK YOU HAVE TO BE CAREFULUTION THE DATA, BUT BASING THINGS ON SCIENTIFIC RESULTS IS CLEARLY WHERE THIS IS GOING. I THINK APL1 IS AN EXTREME EXAMPLE BUT I’LL TAKE YOU THROUGH MANY AND SHOW YOU THERE ARE ETHNICSPECIFIC RISK VARIANCES IN THOSE DISEASES. IT’S STRIKING AS AN MD THAT WHEN WE TALK ABOUT BIOLOGIC.

PARAMETERS LIKE KIDNEY FUNCTION AND FILTRATION RATES, NOBODY WOULD ARGUE THERE ARE DIFFERENCES BETWEEN AFRICAN AMERICANS AND EUROPEAN AMERICANS. AS A MATTER OF FACT, WHEN WE USE OUR EQUATIONS TO CALCULATE KIDNEY FUNCTION, IF WE HAVE A 50YEAROLD MALE WITH A CRETE 19 CONSITRATION OF 1, OUR EQUATION VISIT TO ADJUST FOR RACE BECAUSE CREATININE IS PRODUCED BY MUSCLE AND THERE ARE DIFFERENCES IN MUSCLE MASS. IF IT’S A EUROPEAN AMERICAN 52 LIKE ME, YOUR GFR WILL BE 78. THAT SAME CONCENTRATION IN AN AFRICAN AMERICAN IS 95ML PER MINUTE. 17ML PER MINUTE DIFFERENCE!.

SO THIS IS A BIOLOGIC ASPECT OF A PARAMETER WE USE TO MEASURE KIDNEY FUNCTION WHERE NOBODY WOULD ARGUE THAT POPULATIONSPECIFIC DIFFERENCES TWIST. THE TOPICS I WANT TO COVER TODAY AS AN INTRODUCTION, I WANT TO TALK ABOUT AFRICAN RISK TO POOR RESPONSE TO TREATMENT FOR HEPATITIS C. AN AFRICAN AMERICAN PROTECTION FROM IGA NEPHROPATHY, ONE OF THE MOST COMMON KIDNEY DISEASES AFFECTING WORLD POPULATIONS. THESE ARE NOT AREAS WE HAVE WORKED ON. AND THEN I’LL MOVE INTO THE TYPE II DIABETES AND NONDIABETIC NEPHROPATHY, ARTHEROSCLEROSIS AND OSTEOPOROSIS. I WOULD NEVER WANT TO START A.

TALK LIKE THIS. I’M GOING TO SPEAK A LOT ABOUT GENETIC AND GENOMIC FACTORS. I’M A BIG BELIEVER FOR THE ENVIRONMENT. AND I DON’T WANT ANYONE TO LEAVE TODAY’S TALK THINKING EVERYTHING THE BASIS OF DISEASE IN ALL PEOPLE IS GENES. BUT THE FACT IS, THAT WE ARE ALL FAR MORE ALIKE THAN DIFFERENT. I WOULD JUST POINT OUT IN ADDITION TO THE ENVIRONMENTAL EFFECTS OF GROWING UP IN A SEPARATED POPULATION GROUP, THIS LESS THAN 1 GENETIC VARIATION CAN CONTRIBUTE PROFOUNDLY TO COMMON COMPLEX DISEASE. AND WE ALL TALK ABOUT DIFFERENT.

DIETS, LIFESTYLES, ATTITUDES, EXPOSURES, STRESSERS AND PERCEIVED STRESSES. THIS IS CRITICALLY IMPORTANT. ACCESS TO HEALTH CARE. I’M GOING TO SHOW YOU DATA IN THE GENERAL AFRICAN AMERICAN POPULATION THERE IS A FAR HIGHER RISK FOR CARDIOVASCULAR DISEASE AND MYOCARDIAL INFARCTION THAN EUROPEAN AMERICANS. WHEN YOU EQUALIZE ACCESS TO HEALTH CARE, THE BIOLOGIC EFFECTS COME OUT WHERE AFRICAN AMERICANS COME OUT WHERE THEY HAVE A 50 LOWER RISK OF MYOCARDIAL. THESE ARE CRITICAL. AS WE ARE LEARNING WITH OTHER IMPORTANT RISK ALLELES, THAT GENE ENVIRONMENT ENTER ACTIONS ARE CRITICAL AND THEY MAY DIFFER.

BASED ON POPULATION GROUPS BECAUSE THE GENETIC PROFILES MAY BE DIFFERENT AND THE ENVIRONMENTAL EXPOSURES MAY BE DIFFERENT AND THIS MAY ALSO CONTRIBUTE TO POPULATIONSPECIFIC DIFFERENCES AND RISK AND THE ENVIRONMENTAL CONTRIBUTORS THERE HOLD OUT GREAT HOPE FOR CURES FOR GENETICALLYBASED DISEASES, ONE OF THE THINGS WE ARE FOCUSING ON. SO THIS IS A TOPIC THAT IS EXPLODING IN RECENT YEARS. THIS IS DATA ON TREATMENT RESPONSE TO HEPATITIS C. PHARMACOGENOMICS, IF YOU MAY. HEPATITIS C IS 170 MILLION CASES WORLDWIDE LEADING CAUSE OF CIRRHOSIS IN NORTH AMERICA AND WE HAVE TREATMENTS INTERFERON.

AND ALPHA AND RIBA VINE BUT THEY ARE VERY TOXIC AND EXPENSIVE TREATMENTS. AFTER TREATMENT, AFTER IDENTICAL TREATMENT COURSES, PATIENTS OF ASIAN AND EUROPEAN ANCESTRY HAVE FAR HIGHER CURE RATES CLEARING THE VIRUS FROM THE CIRCULATION THAN AFRICAN ANCESTRY POPULATIONS. AND THIS IS A VERY IMPORTANT PAPER FROM 2008 IN NATURE BY DAVID GOLDSTEIN’S GROUP AT DUKE, SHOWING GENETIC VARY NATION A SINGLE GENE PREDICTS PRETTY MUCH HALF THE RESPONSE TO INTERFERE ON THERAPY FOR HEPATITIS C. AND WHEN HE LOOKED AT HIS DATA, WHETHER WE WERE TALKING ABOUT EUROPEAN AMERICAN POPULATIONS,.

AFRICAN AMERICAN OR HISPANIC, YOU CAN SEE SUSTAINED VIRAL LONGIC RESPONSE IS FAR HIGHER IN INDIVIDUALS WHO ARE HOMOZYGOUS FOR THE C ALLELE AT THIS SNP AND A GREATER EFFECT WITH THE POORER RESPONSE FOR THE T ALLELE. A LOVELY DOSE RESPONSE BASED ON YOUR GENETIC MAKEUP. SO WHY WOULD AFRICAN AMERICANS RESPOND 50 LESS WELL TO TREATMENT COMPARED TO ASIANS AND EUROPEAN AMERICAN POPULATIONS AND THE ANSWER IS RIGHT HERE. IF YOU LOOK AT THAT PROTECTIVE C ALLELE THAT PORTENDS A GOOD RESPONSE TO TREATMENT, THE FREQUENCY IN EAST ASIAN SANS.

OVER 70. EUROPEAN AMERICANS AND HISPANICS IS 5060 AND AFRICAN AMERICANS IN THE LOW 20. SO THE DISTRIBUTION OF THIS ALLELE EXPLAINS A TREMENDOUS AMOUNT OF THE VARIATION IN TREATMENT RESPONSE OF PHARMACOGENOMIC EFFECT. WE HAVE SEEN THE SAME THING IN IGA NEPHROPATHY. AND I REMEMBER AS WE FOCUSED ON DIABETIC NEPHROPATHY WHICH IS THE LEADING CAUSE OF ADRENAL DISEASE, IT’S UP THERE ON A WORLDWIDE BASIS AND THE INTERESTING THING IS, IT’S LONG BEEN PERCEIVED THAT POPULATIONS OF AFRICAN ANCESTRY ARE AT LOWER RISK FOR IGA NEPHROPATHY. MANY THOUGHT THAT WAS BECAUSE OF.

A LACK OF ACCESS TO HEALTH CARE. THEY WEREN’T GETTING TO KIDNEY DOCTORS IN TIME. THIS IS A DISEASE THAT YOU MUST MAKE BASED ON A KIDNEY BIOPSY. PATIENTS REPRESENT WITH HEMETERIA AND THE HEMETERIA CAN PROGRESS TO PUT NEARIA AND DEVELOPMENT OF CROCKIC KIDNEY DISEASE. CLEARLY IN ASIA, THEY SCREENED SCHOOLAGED CHILDREN WITH URINALYSIS BECAUSE THIS DISEASE IS SO FREQUENT THEY PICK UP HEMETURIA EARLY AND THEY FOLLOW THOSE PATIENTS AGGRESSIVELY AND DO KIDNEY BIOPSIES. BUT IT’S BEEN THOUGHT THAT EUROPEAN AMERICANS ARE IN THE MIDDLE AND AFTER CANS ARE AT LOW.

RISK, ALTHOUGH AGAIN, WE WONDERED IF THIS WAS BECAUSE OF A LACK OF BIOPSY DATA AND ACCESS TO CARE. WELL, A GROUP IN NEW YORK HAS JUST PUBLISHED A PAPER LAST YEAR LOOKING AT VARIATION IN 7 SUSCEPTIBILITY LOCI FOR IGA NEPHROPATHY ACROSS THE WORLD AND IT HAS SHOWN THIS VARIATION EXPLAINS ABOUT 5 OF THE RISK FOR DEVELOPMENT OF IGA NEPHROPATHY. BUT THIS IS A STANDARDIZED PLOT AND YOU CAN SEE A DISTRIBUTION OF THE NUMBER OF RISK VARIETIES IN THESE 7 GENES ASSOCIATED WITH IGA NEVERROPY THAT OF THE SO FOR.

EUROPEAN ANCESTRY POPULATIONS IN YELLOW, YOU SEE A NICE BELLSHAPED CURVE AROUND THE MIDPOINT OF THE IF YOU LOOK AT ASIAN POPULATIONS IN RED, IT IS SKEWED TO THE RIGHT WITH EXCESS NUMBERS OF RISK VARIANTS AND IF YOU LOOK AT AFRICAN ANCESTRY POPULATIONS, IT IS SKEWED WAY TO THE LEFT WITH A LOW FREQUENCY OF RISK VARIANTS. AND IF WE LOOK AT A HEAT MAP, YOU CAN SEE ALL ACROSS ASIA THE HIGHEST PREVALENCE OF DISEASE AND THE HIGHEST NUMBER OF RISK VARIANTS WITH A GRADED EFFECT THROUGHOUT ASIA OR THROUGHOUT.

EUROPE AND INTO AFRICA WHERE THE FREQUENCY OF DISEASE IS FAR LOWER AND AFRICAN AMERICANS ARE FAR LESS FREQUENTLY EFFECTED. SO INTERESTINGLY, IT’S EASIER IN MY MIND, TO PICK UP AN AFRICAN ANCESTRY PROTECTIVE EFFECT THAN RISK EFFECT BECAUSE THE ENVIRONMENT COMPLICATES RISK. LOW OR POOR ACCESS TO CARE, LOW SOCIOECONOMIC STATUS ARE ASSOCIATED WITH RISKS AS ARE RISK VARIANTS. HERE IS A EXAMPLE OF LOW FREQUENCY OF RISK VARIANTS IN AFRICAN ANCESTRY POPULATIONS. SO THESE TWO EXAMPLES OF HELP TITIS C AND IGA NEPHROPATHY PROVE THE POINT. I WANT YOU TO BE AWARE OF WHAT A.

TREMENDOUS SHIFT IN THE PARADIGM THIS IS. THIS IS A NEW THINK LAND JOURNAL OF MEDICINE SOUNDING BOARD FROM 2003. NOT 10 YEARS AGO. AND I REMEMBER READING THIS PAPER ON A PLANE WHERE IT SAID, MINORITY GROUPS, PARTICULARLY BLACKS IN THE UNITED STATES, ARE ASSUMED TO BE GENETICALLY PREDISPOSED TO VIRTUALLY ALL COMMON CHRONIC DISEASES. GENES ARE REGULARLY PROPOSED AS THE CAUSE WITHOUT GENETIC DATA AND THE SOCIAL AND BIOLOGIC FACTOR ARE HOPELESSLY CONFOUNDED. THAT WAS A LITTLE DEPRESSING. BUT IT WENT ON TO SAY THAT COINCIDENCE IS NOT AN.

EXPLANATION. THE CORRELATION BETWEEN UNSUPPORTED GENETIC INFERENCE AND SOCIAL STANDING OF A GROUP IS FLARING EVIDENCE OF BIAS AND DEMONSTRATES HOW RACE CAN BE USED TO CATEGORIZE AND RANK SUBPOPULATIONS. I FOUND THIS APPALLING AND SHOCKING AND I WAS VERY UPSET BY THIS AND I SAID WHO IS DOING THIS STUFF I WENT AND RUSHED TO THE REFERENCE SECTION OF THAT LIST AND THAT FIRST REFERENCE 17, IT WAS OUR WORK. SO, I WANT TO MAKE THE POINT TO YOU THAT IN LESS THAN A DECADE, THE FIELD HAS FLIPPED AND IT’S.

NOW APPRECIATED THAT COMMON RISK VARIANTS ACROSS POPULATION GROUPS CAN ASSOCIATE WITH DISEASE. LET’S START OFF WITH TYPE II DIABETES AND THEN I’M GOING TO WORK MY WAY TO THE FASCINATING RELATIONSHIPS BETWEEN ARTHROSCLEROSIS AND BONE DISEASE. WE WORK PRIMARILY IN DIABETIC POPULATIONS AND I’LL END UP WITH NONDIABETIC KIDNEY DISEASE. THIS IS DATA ON THE PREVALENCE OF TYPE TWO TYPE II DIABETES FROM THE ADA WEBSITE. AND ADULTS BETWEEN 2007 AND 2009, ABOUT 7 OF NONHISPANIC WHITES HAD DIABETES, 12.6 OF NONHISPANIC BLACKS AND 11 OF HISPANICS. SO CLEARLY A HIGH RISK IN THE.

AFRICAN POPULATION. THIS IS DATA THAT WE SUBMITTED TO THE 2013ADA MEETINGS SO THIS DATA IS NOT YET PUBLISHED OF THE WHAT WE DID IS WE TOOK THE RISK ALLELE VARIANCE IN 17 TYPE II DIABETES ASSOCIATED SNIPPS FROM THE MAJOR GWAS ANALYSIS. SO OF THE 50 OR 60 REPLICATED GENES FOR TYPE TYPE II DIABETES, WE TOOK THE MOST REPLICATED AND POWERFUL AND LOOKED AT RISK ALLELE FREQUENCIES IN 2000 EUROPEAN AMERICANS, 800 WITH DIABETES AND 1000 WITHOUT. AND IN 4000 AFRICAN AMERICANS, 2600 WITH DIABETES AND 1400 WITHOUT. AND BY THE WAY, ALL OF THESE.

VICTIMS WERE RECRUITED UNDER THE SAME PROTOCOLS AND SAME GEOGRAPHIC REGION OF THE COUNTRY OVER THE SAME TIME PERIODS. THEY ALL CAME THROUGH MY OFFICE. SO, THERE IS NO DIFFERENCE IN ANY TYPE OF RECRUITMENT PATTERN. AND TO MAKE YOU COMFORTABLE WITH THE GENES WE LOOKED AT, THEY ARE REALLY DIABETES GENES, GAMMA. TCS7L2, THE MOST REPRODUCIBLE DIABETES GENE. KCNJ11, FTO, HNF1 BAIT A NOT MUCH ARGUMENT IN THE DIABETES LITERATURE THESE JEANS AND PATHWAYS PLAY AN IMPORTANT ROLE IN SUSCEPTIBILITY. SO WE SIMPLY TOOK THE 17 GENES WHICH CAN GIVE YOU A MAXIMUM OF.

34 RISK VARIANTS, ONE FROM EACH PARENT AND WE PLOTTED OUT IN AFRICAN AMERICANS WITH DIABETES VERSUS EUROPEAN AMERICANS WITH DIABETES, WHAT ARE THE RISK VARIANT LOADS AND I THINK YOU CAN SEE A SIGNIFICANT KEY VALUE OF 10 TO HAVE MINUS 123. AND HERE IS THE CURVE IN AFRICAN AMERICANS WITH A HIGHER RISK VARIANT LOAD. NOW LOOK VERY CLOSELY BECAUSE I’M GOING CHANGE THE SLIDE. IT’S GOING TO LOOK A LOT SIMILAR. THIS IS THE RISK ALLELE LOAD IN THE NONDIABETICCROSE THAT ARE AFRICAN AMERICAN AND EUROPEAN AMERICAN. THESE PEOPLE DON’T HAVE DIABETES.

AND LET ME GO BACK AND REMIND THAT YOU IN AFRICAN AMERICANS THE RISK VARIANT LOAD IS ABOUT 22 AND IN EUROPEAN AMERICANS WITH DIABETES, IT’S 18. AND WHEN WE JUMP TO THE NONDIABETIC GROUP, IT MOVES TO THE LEFT, IT MOVES DOWN AS WE EXPECT BUT THE POINT IS, THERE IS STILL AN INCREASED RISK LOAD IN NONDIABETIC AFRICAN AMERICANS COMPARED TO NONDIABETIC EUROPEAN AMERICANS. IF WE PUT THIS ALL TOGETHER IN ALL OF THE CASES AND CONTROLS TOGETHER, WE GET A P VALUE OF 10 TO THE MINUS 267 AND I DON’T.

THINK ANYBODY WOULD ARGUE THAT THERE ARE MORE THAN RISK VARIANTS IN GENERAL IN THESE 17 COMMON VARIANTS IDENTIFIED BY GWAS IN AFRICAN ANCESTRY POPULATIONS. SO, INDIVIDUALS WITH TYPE II DIABETES CARRY A HIGHER GENETIC ALLELE RISK LOAD WHETHER THEY ARE AFRICAN AMERICAN OR EUROPEAN AMERICAN. AFRICAN AMERICANS, REGARDLESS OF DIABETES STATUS HAVE HIGHER OVER ALL GENETIC RISK WHICH MAY CONTRIBUTE TO THE HIGH ARE PREVALENCE OF TYPE TWO DIABETES WHEN COMBINED WITH A COMPLEMENTARY ENVIRONMENTAL STIMULI THAT TRIGGERS THIS DIETARY ACCESS. SO WE THINK THAT THERE IS A JETNETIC BACKGROUND LIKE IN IGA.

NEPHROPATHY, A SHIFT OF RISK VARIANTS TO FAVOR DEVELOPMENT OF TYPE II DIABETES IN AFRICAN ANCESTRY POPULATIONS. BUT THAT IS NOT REALLY WHERE I SPENT THE BULK OF MY TIME. I’M A NEPHROLOGIST AND NEPHROLOGISTS ARE NOT ONLY INTERESTED IN KIDNEYS BUT BLOOD VESSELS AND CORONARY ARTERIES AND BONE DISEASE, ALL THESE THINGS EFFECT OUR CKD AND DIALYSIS POPULATION. SO WE HAVE DEVELOPED A SERIES OF STUDIES FIRST STARTED BY DON BOWDEN AND MANY OF THEM ARE NOW JOINTLY BETWEEN DON AND MYSELF, THE DIABETES HEART STUDY FAMILY OF STUDIES WHERE WE HAVE DONE.

SOME OF THE MOST INTENSIVE PHENOTYPING IN SUBJECTS WITH TYPE II DIABETES I’M AWARE OF ANYWHERE. AND JUST TO GIVE YOU A LITTLE OVERVIEW OF THE SAMPLES THAT WE ARE WORKING WITH IN SOME OF THE THESE STUDIES, THE ORIGINAL DIABETES HEART STUDY HAD 1400 SUBJECTS INITIALLY THEY WERE ALL PAIRS, WE WERE LOOKING FOR SIGNIFICANTS WITH TYPE TWO DIABETES AND LATER ON WE BEGAN TO RECRUIT THOSE UNRELATED. WE WANTED TO LOOK AT SUBCLINICAL CORONARY ARTERY DISEASE USING HELICAL CAT SCANS. WHEN DON AND I TALKED, HE SAID AFRICAN AMERICANS HAVE A LOT.

MORE CARDIOVASCULAR DISEASE, WE SHOULD FOCUS ON AFRICAN AMERICANS. I SAID, AS A CLINICIAN, I THINK EUROPEAN ANCESTRY POPULATIONS HAVE MORE CORONARY DISEASE. AND AFTER A LOT OF ARM WRESTLING, WE AGREED TO FOCUS ON EUROPEAN AMERICANS AND HAVE A 15 COMPONENT OF AFRICAN AMERICANS JUST TO ASSESS IF THERE MIGHT BE DIFFERENCES. THE DIFFERENCES IN SUBCLINICAL CORONARY ARTERY DISEASE WERE SO PROFOUND BETWEEN THESE GROUPS AS I’LL SHOW YOU, THAT THAT LED TO THE AFRICAN AMERICAN DIABETES HEART STUDY WHERE ANOTHER 566 AFRICAN AMERICANS WITH TYPE II DIABETES WERE RECRUITED WITH A.

15 FROM HERE WE HAVE ABOUT 750 AFRICAN AMERICANS, 1200 EUROPEAN AMERICANS. ALL OF THESE SUBJECTS HAVE CT MEASURES OF CORONARY ARTERY CALCIFIED PLAQUE, CAROTID ARD RECALESCESSIFIED PLAQUE. BONE DENSITY IN THE THORACIC AND LUMBAR VERTEBRAE. FAT AT POSE TISSUE VOLUMES AROUND THE HEART SUBCUTANEOUS, INTRAMUSCULAR, VISCERAL, KIDNEY FUNCTION AND A WHOLE HOST OF INFLAMMATORY PARAMETERS AND MARKERS. SO, THIS IS AN EXTRAORDINARILY WELL PHENOTYPED STUDY TO WHICH WE WERE THEN FORTUNATE ENOUGH TO DO CEREBRAL MRIIs AND COGNITIVE FUNDS TESTING TO LINK CORONARY DISEASE AND CEREBRAL MACRO VASCULAR DISEASE FOR BLOOD.

VESSELS THROUGHOUT THE BODY AND RECENTLY STARTED IT LONGITUDINAL WHERE WE ARE BRINGING BACK 300 OF THESE PEOPLE TO LOOK AT CORONARY ARTERY CALCIUM PROJECTION I’M GOING TO SHOW YOU SOME OF THE FAT FACING RELATIONSHIPS BETWEEN VITAMIN D, BONE DISEASE AND CALCIFIED PLAQUE. SO THIS IS THE FRAMEWORK WE WORK IN IN THE CARDIOVASCULAR REALM SEPARATE FROM THE NEPHROPATHY. AND I WANT TO PREFACE THIS BY SAYING, HIGHER RATES OF MYOCARDIAL I THINK FARCTION AND CARDIOVASCULAR DISEASE ARE CLEAREDY SEEN IN AFRICAN AMERICANS RELATIVE TO EUROPEAN AMERICANS. AND A LOT OF THIS REFLECTS.

UNFORTUNATELY ACCESS TO HEALTH CARE. AND SOCIOECONOMIC STATUS. NO ARGUMENT ABOUT THAT. BUT I DON’T KNOW IF YOU’RE AWARE THAT WHEN YOU LOOK AT POPULATIONS LIKE THE VETERAN ADMINISTRATION POPULATION, KAISER PERMANENTE HMO, AND THE MEDICARE OR CMSESRD PROGRAM, THE DIALYSIS PROGRAMS, EVERY TIME YOU NORMALIZE CARE AND EQUALIZE ACCESS TO CARE, SIGNIFICANTLY LOWER RATES OF MYOCARDIAL INFARCTION ARE OBSERVED IN AFRICAN AMERICANS RELATIVE TO YOU EUROPEAN AMERICANS. THE DIFFERENCES ARE 50 LOWER RISK OF MI IN THE DIALYSIS POPULATION IT’S STRIKING THAT AFRICAN AMERICANS SEE A NEVERROLOGIST LATER IN THEIR.

COURSE, WE THINK THEY HAD DISPARITIES IN CARE FOR THEIR WHOLE LIVES. BUT IF YOU JUST REVERSE THESE THINGS FOR A FEW YEARS, YOU START TO SEE THE BIOLOGY COME THROUGH. SO THIS IS A FASCINATING PAPER IN THE VA POPULATION BY Dr. YOUNG FROM 2003. THIS STUDY HAD 430,000 SUBJECTS WITH TYPE II DIABETES. AND I WANT YOU TO SEE HERE THEY MAKE THE POINT THAT ALL MINORITY POPULATIONS, AFRICAN AMERICANS, ASIANAMERICANS, NATIVE AMERICANS, HAVE LOWER RISKS OF CARDIOVASCULAR DISEASE COMPARED TO EUROPEAN AMERICANS. AND THIS IS A MAJOR CABLE FROM.

THE PAPER. THE CAUCASIAN GROUP ALONG THE DOP IS NORMALIZED TO A RISK OF ONE. AND WHEN WE ARE LOOKING FOR KIDNEY DISEASE END STAGE RENAL DISEASE OR DIABETIC NEPHROPATHY, AFRICAN AMERICANS IN THE TWO OR THREE YEAR PERIOD THEY WERE FOLLOWED IN THIS STUDY HAD A SIGNIFICANTLY HIGHER RISK OF KIDNEY INVOLVEMENT THAN EUROPEAN AMERICANS, JUST AS WE EXPECTED. JUST AS WE SEE IN THE U.S. BUT IF WE LOOK AT THE RISK OF CARDIOVASCULAR DISEASE OR MYOCARDIAL INFARCTION, THERE IS A ODDS RATIO OF.51. HALF THE RISK IN AFRICAN.

AMERICANS COMPARED TO EUROPEAN AMERICANS AT THE SAME TIME WE SEE EXCESS RATES OF KIDNEY DISEASE. THIS IS TRUE OF ALL THE MINORITY POPULATIONS, LOWER CARDIOVASCULAR A LITTLE WHEN CARE IS EQUALIDES. IF YOU DON’T LIKE THIS STUDY AND YOU WANT TO LOOK AT KAISER, THIS IS ANOTHER STUDY THAT HAD A TOTAL OF 62,000 PATIENTS CAME TO EXACTLY THE SAME CONCLUSION. 50 LOWER RISK OF HEART ATTACK IN THIS HMO IN AFRICAN AMERICANS COMPARED TO EUROPEAN AMERICANS AND THE SURVIVAL ON DIALYSIS IS STRIKINGLY HIGHER IN AFRICAN AMERICANS THAN EUROPEAN.

AMERICANS, AND BELIEVE ME, IT’S DUE TO REDUCTIONS IN CARDIOVASCULAR DISEASE. SO, WHAT WE HAVE BEEN MEASURING IN THESE DIABETES HEART STUDY FAMILY OF STUDIES IS A HELICAL CAT SCAN WITH NO CONTRAST, AND THIS WHITE LINE YOU SEE HERE IS ACTUALLY CALCIUM IN THE LEFT MAIN AND CIRCUMFLEX CORONARY ARTERIES. NOW THE PRESENCE AND SEVERITY OF CAMSIFIED PLAQUE IS A STRONG PREDICTOR OF CARDIOVASCULAR DISEASE AND DEATH NO MATTER WHAT YOUR POPULATION GROUP, NO MATTER WHAT YOUR THE NECESSITY. AND WE HAVE SHOWN ETHNICITY. IF YOU ADD THIS TO FRAMINGHAM.

RISK SCORE IT MAY BETTER STRATIFY WHO NEEDS MORE INTENSIVE THERAPY. SO THIS CLEARLY REFLECTS ARTHROSCLEROSIS. AND IN THE DIABETES HEART STUDY WITH THE EUROPEAN AMERICAN PATIENTS, I HAVE TO TELL YOU, EVERY WEEK I WAS GETTING TWO OR THREE PANIC SCORES FOR CORONARY ARTERY CALLSIUMS LEVELS, 1000, 10,000, WE SEEN 12,000 IN SOME OF OUR PATIENTS WHO WERE ASYMPTOMATIC AND JUST COMING IN FOR A CAT SCAN. AS I DO THIS STUDY IN THE AFRICAN AMERICAN HEART STUDY I RARELY GET A CALL WHEN IT’S OVER 1000. THE DIFFERENCES ARE STRIKING.

WHEN WE COMPARE THE 2000 SUBJECTS IN THE DIABETES HEART STUDY FAMILY OF STUDIES, OUR AFRICAN AMERICAN POPULATION HAVE HIGHER FASTING BLOOD SUGARS AND HIGHER HEMOGLOBIN A1C. HIGHER BLOOD PRESSURE, MORE ALBUMIN IN THE URINE, WHICH IS A MAJOR CARDIOVASCULAR RISK FACTOR. HIGHER LD R AND HIGHER PERCENTAGE OF CURRENT AND FORMER SMOKERS WHICH SHOULD INCREASE YOUR RISK, CONVENTIONAL RISK FACTORS FOR HEART DISEASE. YOU KNOW AFRICAN AMERICANS HAVE LOWER TRIGLYCERIDES AND HIGHER HDL CHOLESTEROL WHICH WILL BE PROTECTIVE. BUT THE QUESTION IS, HOW MUCH DO ALL OF THESE FACTORS FEED IN.

WHAT ARE THE CORONARY ARTERY SCORES IN THESE POPULATIONS AND THE DIFFERENCE DIFFERENCES ARE AMAZING IN THE EUROPEAN AMERICAN MEN, THE MEDIAN CORONARY ARTERY CALCIUM WAS 1300. IN THE AFRICAN AMERICAN MEN, THE MEDIAN SCORE WAS 166. EIGHT TIMES LOWER IN SPITE OF ALL OF THESE ACCESS CONVENTIONAL RISK FACTORS. AMONG WOMEN IT’S LESS PRONOUNCED AND 2.5 FOLD LOWER AND THE DIFFERENCE WERE SO STAGGERING THAT THIS IS WHAT LED TO PERFORMANCE OF THE AFRICAN AMERICAN DIABETES HEART STUDY TO EXPLAIN THIS RELATIVE PROTECTION FROM CALCIFIED PLAQUE THAT DOES CHANGE THEM TO REDUCTIONS AND.

EVENTS WHEN YOU HAVE EQUAL ACCESS TO HEALTH CARE. WHAT I WANT TO TALK ABOUT NOW IS THE TOOL THAT WE AND OTHERS USED AND FRANKLY, I HAVE TO CREDIT MANY FOLKS HERE AT NIH, MICHAEL SMITH, JEFFREY COP, SHERRY WINKLER AND GEORGE NELSON. WE HAVE APPLIED REGIONAL ADD MIXTURE MAPPING WHICH IS A GENETIC MAPPING TOOL FOR GENE DISCOVER IN ADD MIXED POPULATIONS. AFRICAN AMERICANS ARE AN ADD MIXED POPULATION WITH APPROXIMATELY 80 AFRICAN ANCESTRY AND 20 EUROPEAN ANCESTRY ON AVERAGE ACROSS THE UNITED STATES. AND IF THERE ARE DISEASECAUSING.

VARIANTS THAT ARE PRESENT MORE FREQUENTLY IN AN AT RISK POPULATION GROUP EITHER THE GROUP OF EUROPEAN ANCESTRY OR AFRICAN ANCESTRY, AND WE ARE LOOKING FOR REGIONS OF THE GENOME ENRICHED FOR THE ANCESTRAL POPULATIONS THAT CARRY ACCESS RISK OF DISEASE. THIS CAN BE DONE AT FAR LESS EXPENSE THAN A TRADITIONAL GWAS, 1500 CAREFULLY SELECTED MARKERS THAT HAVE MARKEDLY DIFFERENT ALLELE FREQUENCIES BETWEEN POPULATION GROUPS CAN SCREEN THE GENOME AND THIS IS WHAT LED TO IDENTIFICATION OF APL1. IF THE RISK DISEASE IS EUROPEAN AND ANCESTRY SAY ARTHROSCLEROSIS OR CALCIFIED PLAQUE, YOU EXPECT.

AFRICAN AMERICANS WITH HIGH LEVELS OF CORONARY ARTERY CALCIUM TO HAVE ACCESS EUROPEAN ANCESTRY IN CERTAIN REGIONS OF THE GENOME CARRYING RISK ALLELES. IF THE DISEASE IS NEPHROPATHY OF AFRICAN ANCESTRY BECAUSE AFRICAN AMERICANS HAVE FAR MORE NEPHROPATHY THAN CAUCASIANS, YOU EXPECT IT IN THAT REGION. THIS IS A FIGURE I STOLE FROM MIKE SMITH’S REVIEW PAPER. IF WE HAVE POPULATION A, LET’S JUST SAY THAT THIS IS A EUROPEAN POPULATION IN B AND AFRICAN POPULATION, WITH EARLY ADD MIXTURE AND RECOMBINATION, LARGE CHUNKS OF THE GENOME RECOMBINED AND OVER MULTIPLE POPULATIONS,.

THE RECOMBINATIONS BECOME SMALLER AND SMALLER AND WE CAN TAG THEM WITH VARIANTS THAT HAVE TREMENDOUSLY DIFFERENT ALLELE FREQUENCIES ACROSS POPULATION GROUPS. WE COMPARE A CASE GROUP WITH DISEASE VERSUS CONTROL GROUP WITHOUT DISEASE AT THE SAME MARKER. WE ARE LOOKING FOR DIFFERENCES IN ANCESTRAL POPULATION RISK AT THAT VARIANT THAT WOULD GO WITH DISEASE. SO, IF THE DARK BLUE HERE IS AFRICAN ANCESTRY AND THE DOTTED LINE IS EUROPEAN OR IS EXCUSE ME, IF THE DARK BLUE LINE IS CASES AND THE DOTTED LINE IS CONTROLS, AND WE SEE A REGION.

WITH ACCESS AFRICAN ANCESTRY, THAT CHROMOSOMAL REGION WOULD LIKELY BE ASSOCIATED WITH A KIDNEY DISEASE VARIANT WITH ENDSTAGE RENAL DISEASE AS THE PHENOTYPE. IF IT GOES THE OTHER WAY AND REDUCTION IN AFRICAN ANCESTRY, THAT WOULD BE A EUROPEANDERIVED RISK VARIANT. THE PREMISE IS SIMPLE. YOU ONLY NEED 1500 MARKERS TO SCAN THE GENOME. AND THIS IS A PAPER THAT OUR GROUP PUBLISHED IN THE LAST FEW WEEKS WHERE WE PERFORMED ADD MIXTURE MAPPING FOR CORONARY ARTERY CALCIFIED PLAQUE IN AFRICAN AMERICANS FROM THE AFRICAN AMERICAN HEART STUDY AND INCLUDED SUBJECTS WITH DIABETES.

FROM MESA AND DHS. WE ENDED UP WITH 1,40 CASES 1,040 CASES. THE MACE STUDY HAD ALREADY PUBLISHED MESA STUDY AFTER CANS AMERICAN WITH HIGHER LEVELS OF CALCIFIED PLAQUE HAD HIGHER LEVELS OF OVERALL EUROPEAN ANCESTRY WHICH FIT WITH WHAT WE SAW ON THE HELICAL CT SCANS AND THE DATA FROM THE VA AND KAISER AND THE DIALYSIS REGISTRIES. SO WE TOOK THIS ANOTHER STEP AND LOOKED FOR WHERE IN THE GENOME WAS THIS EUROPEAN ANCESTRY AND THE RESULTS ARE FAIRLY STRIKING. OVERALL 1,040 SUBJECTS, AFRICAN ANCESTRY WAS 80.

IN THE GROUP THAT HAD PRESENCE OF CORONARY ARTERY CALCIFIED PLAQUE, SO GREATER THAN 10 IS PRESENT. YOU CAN SEE THERE WAS 21 EUROPEAN ANCESTRY. IN THE GROUP WITH NO CORONARY ARTERY CALCIUM, 19 EUROPEAN ANCESTRY. AND THAT DIFFERENCE HELD AFTER YOU ADJUSTED FOR AGE, GENDER, THE DIFFERENT STUDIES, WHETHER WE LOOKED AT PRESENCE OR ABSENCE OF CORE NARR’S CALCIUM OR AS A QUANTITATIVE TRAIT. BUT WE IDENTIFIED 11 REGIONS IN THE GENOME, THREE OF WHICH WERE GENOMEWIDE SIGNIFICANT BY ADD MIXTURE MAPPING FOR CORONARY ARTERY CALCIUM AND EIGHT OTHERS STRONGLY SUGGESTIVE WITH A SCORE.

OF GREATER THAN 2.5. 1111 REGIONS DEMONSTRATED EXCESSIVE EUROPEAN ANCESTRY. THERE WASN’T ONE SINGLE REGION ASSOCIATED WITH CORONARY ARTERY CALCIUM IN AFRICAN AMERICANS WITH AFRICAN ANCESTRY. SO THIS IS THE LIVE SCORES FOR THESE 11 REGIONS AND YOU CAN SEE 3.7, 3.0 AND 3.4. THE TOP LIVE SCORE ON CHROMOSOME 1 IS IN THE GL. LYS1 GENE AND I’LL TALK ABOUT THE RELATIONSHIPS BETWEEN BONE AND CORONARIALS YUM WHICH WHICH IS FROM TRANSFORMATION OF THE BLOOD VESSEL CELLS AND GLYS1 REG LADIES BONE MOREOVER JENNETIC PROTEIN GENES. WE ARE VERY EXCITED ABOUT THESE.

REGIONS. THE POINT I WANT TO MAKE IS THAT EVERY SINGLE ONE OF THESE REGIONS IS A HIGHER FREQUENCY OF RISK ALLELE VARIANTS IN THE GROUP WITH CORONARY ARTERY CALCIUM AT THE PRESENT VERSUS ABSENT IT’S STAGGERING. 1111. SO I THINK ADD MIXTURE MAPPING IS AN EXCITING TOOL FOR THIS TRAIT AND WE ARE FINE MAPPING THESE REGIONS AND TRYING TO HONE IN ON RISK VARIANTS AND THESE ARE BROAD LINKAGETYPE PEEKS SO WE HAVE TO FIND THAT AND GET DOWN TO EXACTLY WHERE THE ALLELES ARE. BUT THERE IS ANOTHER EXAMPLE OF.

A HIGHER RISK VARIANT BURDEN FROM EUROPEAN ANCESTRY IN THE AFRICAN AMERICAN POPULATION THAT CONTRIBUTE TO CORONARY DISEASE. I SHOULD MENTION THAT THE CHROMOSOME 9P, WHICH WE PICKED UP ON MALL MAPPING IS THE SAME THAT IS ASSOCIATED WITH CORONARY ARTERY DISEASE OF EUROPEAN POPULATIONS. THIS REGION IS NOT ONLY ORBITED ASSOCIATED WITH MI BUT OR NARY ARTERY IN EUROPEAN POPULATIONS AND ALSO PLAYING A ROLE IN AFRICAN ANCESTRY POPULATION SYSTEM. SO A VERY EXCITING TOO AND WE HOPE TO BE ABLE TO HONE DOWN THE ETHNIC DIFFERENCES AND SUSCEPTIBILITIY WITH THOSE DATA.

AND I WANT TO TALK TO YOU ABOUT A HOT TOPIC IN THE WORLD, VITAMIN D, OSTEOPOROSIS, BONE DISEASE, AND ASSOCIATED CARDIOVASCULAR RISK. WELL SO, WE ALL NEED TO BE AWARE THAT THERE IS AN OPPOSING RELATIONSHIP BETWEEN BONE MINERAL DENSITY AND CALCIFIED ANOTHERSTERROTIC PLAQUE OR SUBCLINICAL ARTHEROSCLEROSIS. INDIVIDUALS WITH OSTEOPOROSIS HAVE MARKEDLYILY HIGHER LEVELS OF CORONARY ARTERY CALCIUM, DOESN’T MATTER IF YOU’RE BLACK OR WHITE OR IF IT’S DONE IN A LONGITUDINAL STUDY OR CROSS SECTIONAL. NO PAPER THAT HAS BEEN PUBLISHED THAT DISPUTES THIS OPPOSING RELATIONSHIP. AND AGAIN, THERE IS SOME.

PHYSIOLOGY BEHIND IT. VASCULAR SMOOTH MUSCLE CELLS TAKE ON A PROGRAMMED CELL LIKE AN OSTEOBLAST IN BONE. SO DO ETHNICSPECIFIC RELATIONSHIPS EXIST BETWEEN BONE AND VASCULAR HEALTH A AS A NEPHROLOGIST, WE LOVE THINGS ALL MINERAL AND ELECTROLIGHT AND BONE. BUT ONE OF THE SMARTEST THINGS THAT WAS DONE IN THE DIABETES HEART STUDIES IS BY Dr. JEFFREY CAR, RADIOLOGIST AT WAKE FOREST E HE PUT THIS PHANTOM UNDER ALL THE CT SCANS SO WHILE SCANNING THE HEART FOR CORONARY CALCIUM OR AORTA, WE HAVE A PHANTOM WE CAN MEASURE THORACIC AND LUMBAR BONE MINERAL.

DENSITY ON THE HELICAL CT. SO WE WERE MEASURING SIMULTANEOUS ARTHEROSCLEROSEIS AND BONE DENSITY. I’M PERPLEXED AS TO WHY OTHER STUDIES HAVE NOT LOOKED AT BONE DENSITY. WE ALSO LOOK AT FAT VOLUMES ON THESE SCANS AS WELL. AND THE POINT THEY WANT TO MAKE IS THAT THE VITAMIN D ACCESS BONE HEALTH IS TREMENDOUSLY DIFFERENT BASED ON ETHNICITY. SO FOR EXAMPLE, RELATIVE TO EUROPEAN AMERICANS, AFRICAN AMERICANS HAVE FAR LOWER, 25 HYDROXY VITAMIN D LEVELS. IS IT A PROBLEM I DON’T THINK IT’S A PROBLEM. I THINK IT’S LIKE GFR.

IT’S A TOTALLY DIFFERENT SCALE IN AFRICAN ANCESTRY POPULATIONS AND IT’S NOT JUST FROM HAVING DARKER SKIN WITH LESSER ACTIVATION OF VITAMIN D IN THE SKIN. AFRICAN AMERICANS HAVE HIGHER ACTIVE 125 DIHYDROXY VITAMIN D LEVELS THAN EUROPEAN POPULATIONS AND LOWER RATES OF OSTEOPOROSIS AND THAT IS DESPITE THE FACT THAT THEY HAVE LESS DIETARY CALCIUM INGESTION AND TREMENDOUS LEELEEER VITAMIN D LEVELS. SO IF YOU HAVE A LOW VITAMIN D LEVEL IN AN AFRICAN AMERICAN WHY ARE WE SUPPLEMENTING IT IF THEIR BONES ARE HEALTHY THAT’S THE TREATMENT OF VITAMIN.

D IS TO KEEP YOUR BONES HEALTHY. IF THERE IS NO BONE DISEASE, DON’T TREAT A NUMBER. THE RANGE IS PHYSIOLOGICALLY DIFFERENT. WE TALKED ABOUT THE FACT THAT CORONARY ARTERY CALCIUM AND VASCULAR CALCIUM IS MUCH LESS IN AFTER CANS THAN EUROPEANS BUT INCREASED RENAL TUBULAR CALCIUM REABSORPTION AND FAR LES CALCIUM IS IN THE URINE AND THEY HAVE FEWER CALCIUM CONTAINING KIDNEY STONES. AFRICAN AMERICANS HAVE HIGHER EFFECTS OR HIGHER LEVELS OF IN TACT PARATHYROID HORMONES, THAT BREAKS DOWN BONE TO RELEASE CALCIUM AND PHOSPHORUS EXCEPT THEIR BONES ARE RESIST WANT TO.

THE PT. AND THEY DON’T BREAKDOWN THEIR BONES. SO EVERYTHING THAT REGULATES VITAMIN D, CALCIUM, BONE METABOLISM, IS ON A TREMENDOUSLY DIFFERENT SCALE IN AFRICAN AND EUROPEAN ANCESTRY POPULATIONS AND I THINK THAT MANY NEPHROLOGISTS AND ENDOCRINOLOGISTS FAIL TO APPRECIATE THIS AND THINK ABOUT ONE NORMAL RANGE FOR VITAMIN D. WELL, IN OUR AFRICAN AMERICAN DIABETES HEART STUDY, WE FOUND SHOCKING RESULTS. NUMBER 1, WHEN WE LOOK AT 25 HYDROXY VITAMIN D LEVELS, WE SEE THAT I SHOULD SAY WE HAVE NOT LOOKED AT VITAMIN D IN THE WHITES BUT THERE IS A PERCEPTION.

THAT VITAMIN D WOULD PROTECT FROM ARTHROSCLEROSIS AND THERE IS VERY LITTLE DATA TO SUPPORT THIS BUT THERE IS A FEELING IN THE GENERAL COMMUNITY THAT LED TO THE INSTITUTE OF MEDICINE REPORT LAST YEAR SAYING THERE IS NO DATA FOR ATH SCLEROSIS OR CANCER PROTECTION FROM GIVING VITAMIN D. YOU GIVER IT FOR BONE DISEASE. BUT NO CONCERN THAT VITAMIN D WAS BAD FOR BLOOD VESSELS. IN THE AFRICAN AMERICAN DIABETES HEART STUDY WE SAW POSITIVE RELATIONSHIPS BETWEEN 25 VITAMIN D AND CORONARY ARTERY CALCIUM. 500 AFRICAN AMERICANS WE STUDIED.

I THINK LESS THAN 10 WERE ON SUPPLEMENTAL VITAMIN D. THIS WAS JUST THEIR BASELINE CIRCULATING VITAMIN D LEVELS. THE HIGHER THE LEVEL, I HIGHER THE CORONARY CALCIUM. WE CAUTIONS GENERAL INTERNISTS AND FAMILY DOCTORS SHOULD NOT BE SUPPLEMENTING VITAMIN D WITHOUT BONE DISEASE BECAUSE YOU MIGHT BE WORSENING ATHLERO SCLEROSIS. IT’S KNOWN IN EUROPEAN POPULATIONS THAT HIGH VITAMIN D LEVELS ASSOCIATE WITH HIGHER BONE DENSITY. IN THE AFRICAN AMERICAN DIABETES HEART STUDY, THE HIGHER THE VITAMIN D LEVELS, THE LOWER THE BONE DENSITY. PEOPLE THOUGHT WE WERE CRAZY. UNTIL THE WOMEN’S HEALTH.

INITIATIVE PUBLISHED DAY DITA THAT IN WHITE WOMEN SUPPLEMENTING VITAMIN D, HIP FRACTURES WENT DOWN IN AFRICAN AMERICAN WOMEN, SUPPLEMENTING HIP FRACTURES WENT UP. SO THERE IS AN ETHNIC DIFFERENCE IN RESPONSE TO VITAMIN D AND BONE HEALTH AND BECAUSE OF THAT INVERSE RELATIONSHIP, WE WORRY ABOUT REGIONS IN THE GENOME THAT MAY REGULATE COINCIDENTALLY BONE HEALTH AND CORONARY DISEASE RISK. GLYS1 IS A GENE HOLDING UP IN THE FINE MAPPING AND COULD REGULATE BMP2 AND BE A GREAT LINK. SO THESE ARE VERY COMMON DISEASES. OSTEOPOROSIS, ARTHROSCLEROSIS, TYPE II DIABETES AND WE HAVE TO.

LOOK AT POPULATIONSPECIFIC RISK DIFFERENTLY IN AFRICAN ANCESTRY POPULATIONS. BUT I WANT TO END IN WHAT I SHOULD BE TALKING ABOUT AS A NEPHROLOGIST AND THIS IS AN AFRICAN AMERICAN PATIENT ON DIALYSIS. AND THE STORY IS FASCINATING. YOU’RE AWARE OF THIS DATA. IN THE U.S. DATABASE, THE POPULATIONS RISK FOR EN STAGED RENAL DECEASE IS FOURFOLD HIGHER IN AFRICAN POPULATIONS COMPARED TO EUROPEAN POPULATIONS. EUROPEAN POPULATIONS HAVE THE LOWEST RISK OF ETCHED OF THE NATIVE AMERICANS, ASIANAMERICANS, HISPANIC AND AFTER CANS HAVE MORE RISK FOR KIDNEY DECEASE. WHEN WE LOOK AT HIV NEPHROPATHY,.

THE AFRICAN AMERICAN AND EUROPEAN RISK MAY BE 50 FOLD HIGHER. A LOT OF THIS IS ATTRIBUTED TO ENVIRONMENT AND LACK OF ACCESS TO CARE BUT WE WERE VERY EARLY ON INTERESTED IN FAMILIAL CLUSTERING OF KIDNEY DISEASE. FOR THOSE GENETICISTS IN THE AUDIENCE THIS MUST BE UP SWING BECAUSE ONLY THE MEN ARE EFFECTED IN THIS FAMILY. AND THIS IS FROM A SERIES OF PAPERS WE DID IN AFRICAN AMERICAN POPULATIONS IN THE EARLY 90s. THERE WAS A DISEASE CALLED HYPERTENSION ATTRIBUTED NEPHROPATHY WHICH WE NEVER BELIEVED WAS CAUSED BY HIGH.

BLOOD PRESSURE BUT IT WAS NONDIABETIC SUBJECTS WHO GENERALLY HAD LOW LEVELS OF PROTEIN IN THE URINE AND DIDN’T GET A KIDNEY BIOPSY. THAT’S WHAT IT WAS. AND WE LOOKED AT AFRICAN AMERICANS WITH TYPE TYPE II DIABETES AND NEPHROPATHY AND LINE UP US AND HIV AND THIS IS IN THE PREHEART ERA SO THIS WAS ESSENTIALLY UNTREATED HIV. WHAT WAS STRIKING IS THESE WERE PATIENTS NEW TO DIALYSIS, 2440 OF THEM REPORTED HAVING OTHER RELATIVES WHO WERE ON DIALYSIS AT SOME POINT IN THEIR LIFE, FIRST OR SECOND DEGREE RELATIVES.

AMAZING FAMILY CLUSTERING AND WE LOOKED AT AFRICAN AMERICANS WITH THE SAME DEGREES OF HYPERTENSION, DIABETES, HIV INFECTION WHO AFTER A PROLONGED COURSE DID NOT GET RENAL INVOLVEMENT AND WE ASKED ABOUT THEIR FAMILIES. HYPERTENSIVE AFTER CANS AMERICANS 8 HAD A RELATIVE ON DIALYSIS. DIABETES, 7, INDEX CASE LACKED NEPHROPATHY. LUPUS, WITH ANTINUCLEAR BODY DISEASE, RENAL SPARING AND HIV AFTER A LONG PERIOD BUT NO RENAL INVOLVEMENT, ONLY 6 AND NONE, 7 AND 8 HAD A RELATIVE WITH END STAGE RENAL DISEASE. IN THE CURRENT ERA, 7 OF ALL AFRICAN AMERICANS WILL BE ON END.

STAGE RENAL DISEASE REPLACEMENT THERAPY AT SOME POINT IN THEIR LIFE. 2 FOR WHITES. SO THESE GROUPS WITH THE SAME HIGH BLOOD PRESSURE DIABETES AND HIV INFECTION LOOKED LIKE THE BACKGROUND POPULATION BUT THE MINUTE THE INDEX CASE HAD NEPHROPATHY, THEIR FAMILIES WERE FLUSH. AND BY THE WAY, THIS DOESN’T COUNT RELATIVES WITH CHRONIC KIDNEY DECEASE NOT YET ON DIALYSIS. THIS IS FROM A PAPER WE WROTE IN 1993 AND I THINK THIS IS THE MOST IMPORTANT THING WE EVER FOUND. THESE WERE TYPICAL RUNOFTHEMILL AFRICAN AMERICAN FAMILIES WITH MULTIPLE MEMBERS.

ON DIALYSIS. I KNOW THE PEOPLE IN THESE FAMILIES. AND HERE IS A FAMILY THAT HAD FOUR RELATIVES, THREE BROTHERS AND ONE OF THEIR SONS, FOUR DIFFERENT TYPES OF KIDNEY FAILURE. EVERY FAMILY HAD SOMEBODY WITH KIDNEY FAILURE ATRANSCRIPTED TO HIGH BLOOD PRESSURE, ANOTHER BROTHER WITH DIABETES, GLA MAREULAR DISEASE AND TYPE I DIABETES. THERE ARE FAMILIES HERE WITH HI NEPHROPATHY WHO HAVE HIV NEGATIVE SIBLINGS AND PARENTS ON DIALYSIS FOR OTHER CAUSES. THIS IS VERY COMMON. MANY, MANY AFRICAN AMERICAN FAMILIES HAVE MULTIPLE KIDNEY FAILURE GENES AND THIS LED US TO.

MULTIPLE MEMBERS WITH KIDNEY FAILURE OF DIFFERENT TYPES. AND WE DON’T SEE THIS IN EUROPEAN POPULATIONS, HISPANICS, ASIANS, EVERY FAMILY CLUSTER IS ONE TYPE OF KIDNEY DISEASE. AND THIS LED US TO HYPOTHESIZED THAT THERE WAS AN OVERARCHING KIDNEY FAILURE SUSCEPTIBILITY GENE IN THESE FAMILIES AND THEN IF YOU HAD HIV OR HYPERFLYSEMIA, YOU SCAR YOUR KIDNEYS AND IF YOU LACK THE UNDERLYING GENETIC SUSCEPTIBILITY YOU MIGHT NOT. YOU’RE FAMILIAR WITH THE GWAS AND CANDIDATE GENE ASSOCIATION STUDIES FINDING VERY COMMON VARIANTS OF SMALL EFFECT AND LINKAGE OR FAMILYBASED STUDIES.

FINDING LARGE EFFECT AND IT’S BEEN THOUGHT THAT COMMON VARIANTS ARE RARE AND THAT IS UNLESS THERE IS SELECTION GOING ON AND WE THINK APOL1 IS A GREAT EXAMPLE OF A RISK VARIANT THAT IS SELECTED FOR FOR PROTECTION FROM INFECTION THAT CAUSE KIDNEY DISEASE. AND THIS IS FROM JEFFREY LANDMARK NATURE GENETICS PAPER WE WERE FORTUNATE ENOUGH TO WORK WITH HIM ON AND USING ADD MIXTURE MAPPING, JEFFREY SHOWED A SINGLE PEEK ON CHROMOSOME 22 THAT HAD 10 ACCESS AFRICAN ANCESTRY IN PATIENTS WITH FOCAL GLA MAREULAR SCLEROSIS, FSGS AND.

HIV NEPHROPATHY. THE CONTRIBUTION WE MADE TO THIS IS WE HAD MANY PATIENTS WITH HYPERTENSION ATTRIBUTED NEPHROPATHY ON DIALYSIS THAT WERE NOT KNOWN TO HAVE FSGS, THOUGHT TO HAVE HIGH BLOOD PRESSURE INDUCED KIDNEY FAILURE AND WE SAW STRONG ASSOCIATION IN THIS REGION BETWEEN APOL1 AND MYH9 IN THIS REEGOG ON. AND REGION. IN FATHER WORK THAT HAS BEEN DONE, IT’S SHOWING THAT APOL1 IS THE GENE THAT IS RESPONSIBLE. TWO CODING VARIANTS AND THIS IS A FASCINATING STUDY OF TREPANSOME EXPOSURE TO SERUM FROM AFRICAN AMERICAN INDIVIDUALS BASED ON THEIR APOL1.

GENOTYPE. YOU SEE THIS IS A AFRICAN AMERICAN WITH NO RISK VARIANTS IN APOL1 AND THAT’S A VERY HAPPY AT THE PATSOME SWIMMING WITH A NORMAL LYSOSOME. IF YOU TAKE SERUM FROM INDIVIDUALS WHO HAVE THE G1 RISK VARIANT OR THE G2 RISK VARIANT, YOU SEE LYSOSOMAL AS WELLING BECAUSE WHEN THE PROTEIN IS TAKING UP IT UNFOLDS AND INSERTS INTO THE LYSOSOMAL MEMBRANE AS A CHLORIDE CHANNEL. LYSOSOMAL RUPTURE WITH DEATH OF PARASITE AND PROTECTION. SO ONE COPY OF A G1 OR G2 RISK VARIANT PROTECTION FROM TRIP AN SOMAL INFECTION, TWO COPIES,.

TREMENDOUSLY INCREASED RISK FOR KIDNEY DISEASE. THIS IS AFRICAN SLEEPING SICKNESS IS TRANSMITTED BY AN INFECTED FLY AND THERE IS AN EXAMPLE OF A CANKER SORE AFTER A STING OF A FLY WITH THE TRIPANSOME INFECTED INTO THE SKIN AND IT WILL MAKE ITS WAY INTO THE CIRCULATION. NOW THERE ARE TREMENDOUS CLINICAL APPLICATIONS ON THE HORIZON FROM THIS MAJOR APOL1 DISCOVERY BUT I’LL TELL YOU THAT THE RISK VARIANTS THAT CAUSE KIDNEY DISEASE, THE G1 AND G2 AND WORKING HARD TO FIND OTHER RISK VARIANTS ARE VIRTUALLY LOCKED INTO AFRICAN ANCESTRY.

POPULATIONS AND WE THINK THERE ARE FAIRLY RESENT ORIGIN IN THE LAST 10,000 YEARS. ASIAN POPULATIONS, EUROPEAN POPULATIONS, VIRTUALLY LACK THE G1 AND G2 RISK VARIANTS. THEY ARE JUST NOT THERE. SO, WE NOW KNOW THAT THIS KIDNEY DISEASE THAT IS LONGER BEEN ATRANSCRIPTED TO HIGH BLOOD PRESSURE IS NOT. AND IT’S A RELATIVE OF FSGS IN THE APOL1 FOCAL SIGNIFICANT MENTAL FAMILY, A PRIMARY KIDNEY DISEASE THAT LEADS TO SECONDARY HYPERTENSION. WE KNOW THAT THERE IS APOL1 EXPRESSION IN PHOTO SITES AND THE FIELD IS UP IN ARMS ABOUT WHETHER THE mRNA IS IN.

PROXIMAL TUBE AREULAR EPITHELIAL CELLS AND BLOOD VESSELS. WORK IS ONGOING. APOL1 BINDS TO HDL CHOLESTEROL AND WE DON’T KNOW IF HDL IS IMPACTED CAUSING VASCULAR DISEASE IN THE KIDNEY OR IF APOL DOESN’T BIND AS WELL IF IT’S A RISK VARIANT. SO IT FALSE OFF HD R AND FILTERED AND IT’S TOXIC TO THE TUBULES. SO THIS IS ACTIVE INVESTIGATION. BUT WE CAN ALREADY START TALKING ABOUT GENETICALLY SCREENING HIGHRISK POPULATIONS PREFERENTIALLY AFRICAN ANCESTRY AND KIDNEY TRANSPLANT DONORS AND I CAN SHOW YOU DATA HOW WE CAN TAKE POPULATIONS AND DISSECT OUT.

JUST BASED ON THE POWERFUL EFFECT OF APOL1 FOR NONDIABETIC KIDNEY DISEASE. SO THE FIRST THING THIS FINDING DID IS IT RECLASSIFIED A SPECTRUM OF KIDNEY DISEASES FROM IDIOPATHIC FOCAL SEGMENTEDAL SCLEROSIS AND SCAR TO COLLAPSING FSGS AS WE SEE WITH HIV INFECTION BUT THERE ARE OTHER CAUSES TO THE DISEASE THAT HAS BEEN CALLED FOCAL GLOBAL GLA MAREULAR SCLEROSIS WHICH IS ALL A SPECTRUM. PROTEINURIA, MILD TO MODERATE PRETTY NURRIA, VERY LOW. BUT THEY ARE ALL ASSOCIATED WITH APOL1. TO TELL YOU HOW IMPRESSIVELY, WHEN WE TALK ABOUT GENES, WE.

FIND IN GWAS, THE TCF7L2 GENE IS THE MOST POWERFUL TYPE TYPE II DIABETES GENE, NICOLE IN OUR GROUP FOUND THE CAUSATIVE VARIANT IN TCF7L2 BECAUSE OF THE SMALLER HAPLOTYPE BLOCKS IN AFRICAN AMERICANS. THE ODDS RATIO IS 1.4 WITH A POPULATION ATTRIBUTABLE RISK LESS THAN 5 FOR DIABETES. WHEN WE TALK ABOUT APOL1, FIRST, 12 OF AFRICAN AMERICANS HAVE TWO RISK VARIANTS, ONE FROM THEIR MOTHER AND ONE FROM THEIR FATHER. ‘ HAVE ONE RISK VARIANT SCHOLARSHIP ABOUT 49 DON’T HAVE ANY RISK VARIANTS. THE POPULATION AATTRIBUTABLE RISK FOR NEPHROPATHY IS 70 IN A.

PAPER FROM JEFFREY KOPP. AND PROBABLY WELL OVER 50 FOR HYPERTENSION ATTRIBUTED NEVEROPY THAT. THE ODDS RATIOS ARE 29 FOR HIV NEPHROPATHY AND 17 FOR FSGS AND OVER 7 FOR THE NONDIABETIC NEPHROPATHY. VARIATION IN APOL1 EXPLAINS THE ACCESS RISK FOR NONDIABETIC END STAGE KIDNEY DISEASE IN AFRICAN AMERICANS RELATIVE TO EUROPEANS. IT’S NOT ACCESS TO CARE. IT’S NOT POOR TREATMENT OR BLOOD PRESSURE OR ANYTHING ELSE, WHICH CLEARLY CAN EXIST. BUT IT’S THIS GENETIC VERIFICATION EXPLAINS THE VAST MAJORITY OF THAT EXPRESS RISK AND WE HAVE KNOWN THAT DONOR KIDNEYS FROM INDIVIDUALS OF.

AFRICAN ANCESTRY DON’T SURVIVE AS WELL AFTER KIDNEY TRANSPLANTATION COMPARED TO EUROPEAN DONATED KIDNEYS. APOL1 SEEMS TO FULLY EXPLAIN THAT RISK AS WELL. WHAT IS STRIKING IS THAT WE SEE MUCH WEAKER ASSOCIATIONS WITH MILD NEPHROPATHY ASSOCIATED WITH SEVERE NEPHROPATHY. AND NOT EVERYBODY, NOT ALL OF THE 12 OF AFRICAN AMERICANS WITH TWO RISK VARIANTS WILL GO ON TO GET KIDNEY DISEASE. WE THINK THAT THERE ARE MODULATORS OR SECOND HITS. SO THERE MAY BE A POLONE, SECOND GENE INTERACTIONS WE ARE LOOKING FOR AND OF COURSE THERE ARE ENVIRONMENTAL INTERACTIONS AND.

HIV INFECTION IN THE PREHEART ERA, 50 OF HIV INFECTED SUBJECTS WITH TWO APOL1 RISK VARIANTS GET NEPHROPATHY. SO IT IS CLEARLY A MODIFIABLE RISK FACTOR AND NOW THAT WE HAVE HEART THERAPY, THIS DISEASE IS GOING AWAY. THERE ARE OTHER HIV ASSOCIATED KIDNEY DISEASES WITH COMPLEXES OR CARDIOVASCULAR DISEASE AND LONG TERM SURVIVORS BUT COLLAPSING HIVNEROPATHY IS GOING AWAY WITH HEART THERAPY. SO MODIFYING THE ENVIRONMENT CAN TREAT DISEASE THAT IS GENETICALLY TRANSMITTED. WE ARE NOW LOOKING AT OTHER SECOND HITS WE HAVE SHOWN THAT PATIENTS WITH LUPUS THAT PRO.

GROSS DIALYSIS, BUT NOT MILD NEVERRITIS ARE APOL1 ASSOCIATED AND WE ARE LOOKING AT OTHER VIRUS THAT IS LIVE IN THE KIDNEY LIKE HIV THAT MAY CONTRIBUTE TO PROTECTION OR EXPRESS RISK THAT MAY BE TREATMENT TARGETS. SICKLE CELL NEPHROPATHY OR HEMOGLOBIN IS ANOTHER GENE THAT APPEARS TO INTERACT AND WE NOW SEE A BROAD SPECTRUM OF DISEASES AND I’M CONVINCED THAT THE REASON SOME PEOPLE HAVE FOCAL GLOBAL SCLEROSIS OR COLLAPSE IS DIFFERENT SECOND HITS, DIFFERENT ENVIRONMENTAL FACTORS SER SECOND GENES THAT INTERACT TO GIVE US A DIFFERENT FINAL PHENOTYPE.

TO WRAP UP AND JUST SHOW YOU HOW CLINICALLY USEFUL THIS IS, I WANT TO PRESENT A CASE TO YOU OF A 60YEAROLD AFRICAN AMERICAN WOMAN DIABETICS FOR 10 YEARS, PRETTY NURRIA 4 GRAMS PER DAY. SHE DIDN’T HAVE DIABETIC RETINOPATHY AND A BROTHER WAS ON DIALYSIS WITH NONDIABETIC NEUROPATHY. SHE WAS TWO RISK VARIANT CARRIER AND MY PARTNER WHO THE ON HER FORM, DIABETIC NEPHROPATHY. AND I SAID, THIS WOMAN DOES NOT HAVE DIABETIC NEPHROPATHY. SHE LACKS RETINOPATHY. SHE HAS A BROTHER WITH NONDIABETIC KIDNEY DISEASE AND THE APOL1 RISK GENOTYPE.

SHE NEEDS A KIDNEY BIOPSY. WE WERE BOTH RIGHT. SHE HAD DIABETICNERROPATHY AND HAD COLLAPSING FSGS AND GLA PARALEGAL SCLEROSIS UNRELATED TO DIABETES. WHY IS THIS IMPORTANT IF THE NIDDK WANTS TO DO A TRIAL FOR TREATMENT FOR DIABETIC NEPHROPATHY, DON’T YOU WANT PATIENTS IN THE STUDY WHO HAVE PURE DIABETIC NEPHROPATHY. THESE HAVE COINCIDENT DIABETES BECAUSE AUDIOS COMMON. PROTEINURIA WHICH WE SEE WITH DIABETIC NEUROPATHYIA AND THEY DON’T GET KIDNEY BIOPSIES. MOST OF THE TIME THEY ARE NOT BIOPSIED AND THEY ARE GIVEN A CLINICAL DIAGNOSIS. WE CAN NOW REACH INTO THOSE.

CASES AND GENETICALLY DISSECT CASES OF NONDIABETIC NEPHROPATHY THAT WOULDN’T RESPOND TO THE STUTTEDO TREATMENT AND PULL THEM OUT. SO WITHOUT A KIDNEY BIOPSYIY WOO CAN GENETICALLY DISSECT NONDIABETIC FROM DIABETIC NEPHROPATHY. THIS SI STRIKING PAPER WE PUBLISHED A COUPLE OF YEARS AGO. THESE ARE AFRICAN AMERICAN TRANSPLANTED KIDNEYS FROM DECEASED DONORS. AND THESE ARE THE DECEASED DONOR WHOSE HAD TWO APOL1 RISK VARIANTS AND THEAL GAFF SURVIVAL. THESE ARE THE AFRICAN ANCESTRY DONATED KIDNEYS THAT ARE LESS FOR THE RISK VARIANTS. I HAVE TO TELL YOU, 50 GRAPH LOSS BETWEEN TWO AND 3 YEARS IS.

A BAD OUTCOME. BUT IF YOU LOOK AT AFRICAN ANCESTRY DONATED KIDNEYS THAT DIDN’T HAVE TWO APOL1 RISK VARIANTS, THE SURVIVAL IS IDENTICAL TO EUROPEAN DONATED RISK KIDNEYS. SO IT’S NOT THAT AFRICAN ANCESTRY KIDNEYS ARE NOT GOING TO WORK AS WELL. IT’S KIDNEYS WITH TWO APOL1 RISK VARIANTS ARE NOT GOING TO WORK AS WELL. AND THIS HAS TREMENDOUS CLINICAL IMPLICATIONS BECAUSE WE CAN RAPIDLY SCREEN DONORS AND THESE OUTCOMES ACTUALLY ARE WORSE THAN THE OUTCOMES OF EXPANDED CRITERIA OR KIDNEY DONORS, THAT ARE LESS THAN OPTIMAL BUT PATIENTS NEED A TRANSPLANT SO.

BADLY AND WILL TAKE THAT KIDNEY. THE TWO RISK VARIANT KIDNEYS ARE FAR WORSE THAN ECD KIDNEYS. SO POTENTIAL RECIPIENTS SHOULD KNOW. THEY SHOULD BE INFORMED SO SAY DO YOU WANT THIS SO I THINK THIS HAS A TREMENDOUS CLINICAL APPLICATION AND THEN THE LAST STUTY I’M GO TO SHOW YOU, THIS IS THE AFRICAN AMERICAN STUDY OF KIDNEY DISEASE AND HYPERTENSION TRIAL DATA. YOU ARE ALL VERY FAMILIAR WITH THIS STUDY. THIS WAS PERFORMED ON THE BASIS THAT HYPERTENSION CONTRIBUTED TO DEVELOPMENT OF RENAL FAILURE IN AFRICAN AMERICANS WITHOUT DIABETES AND LOWLEVEL PRETTY.

NURRIA. IF WE CAN USE ENOUGH ACE IN HIP TOR INHIBITOR DRUGS WE CAN TREES THIS WELL. IN THE FIRST THREE YEARS. THE GROUP THAT RECEIVED ACE IN HIP TORS DID A LITTLE BIT BETTER THAN THE GROUP WITHOUT ACE INHIBITORS AND A USUAL BLOOD PRESSURE GOAL. SO IN THREE YEARS THEY WERE SWITCHED TO AGGRESSIVE THERAPY. WHEN I LOOK AT THE NATURAL HISTORY HERE, THIS LOOKS TO ME AND THIS BY THE WAY, THE END POINT IS DEATH DOUBLING OF SERUM CREATININE OR STARTING DEAL SIS AND MOST OF THE ENDPOINTS WERE.

RENAL, NOT DEATH. THE FACT IS THAT 10 YEARS, NEARLY 60 OF PARTICIPANTS WITH AGGRESSIVE THERAPY AND NORMALIZATION OF BLOOD PRESSURE REACHED THE STUDY ENDPOINTED. THIS LOOKS LIKE A PRIMARY KIDNEY DISEASE. THIS LOOKS LIKE FSGS OR SOMETHING ELSE. THIS IS A PAPER THAT HAS JUST BEEN PUSHED IN THE JANUARY KIDNEY INTERNATIONAL WITH JEFFREY KOPP AND SHERIFFY SHERRY WINKLER AND MIKE IN OUR GROUP WHERE WE LOOKED AT APOL ASSOCIATIONS AND ASKED PARTICIPATION VERSUS SYSTEM HEALTHY CONTROLS FROM WAKE FOREST BECAUSE WE NEED HEALTHY CONTROLS. IF YOU LOOKED AT ALL THE.

SUBJECTS WE HAD DNA AVAILABLE, 663, 600 CONTROLS, THE ODDS RATIO IS 2.5 AND P VALUE 10 TO THE MINUS 8. IF WE LOOKED AT THE PEOPLE AND ASKED WHOSE CREATININE ROWS TO GREATER THAN 3 AND WENT ON DIALYSIS, THE ODDS RATIO IS 4.6. AND IF WE LOOK AT THE GROUP WHO STARTED THE STUDY WITH PROTEINURIA 600 MILLIGRAMS A DAY, WHICH IS BY THE WAY NEVER ROTTIC RANGE PROTEINURIA IS 3.5 GRAMS A DAY OR HIGHER. THIS IS 600 MILLIGRAMS A DAY UP TO 2.5 GRAMS. THIS IS RELATIVELY LOWLEVEL PRO.

NEUTERRIA BUT IN THOSE SUBJECTS WHO HAD IT AT BASELINE, THE ODDS RATIO IS 6.3. ONLY 100 OF THOSE SUBJECTS AND 600 CONTROLS TO GET AN ODDS RATIO OF 6.3. THIS IS A POWERFUL EFFECT GENE. IT’S A PROGRESSION GENE. AND THIS IS ACCOMPANYING EDITORIAL FINALLY OTHER PEOPLE IN THE WORLD ARE COMING AROUND TO THE CONCEPT THAT THIS IS HYPERTENSION MISATTRIBUTED KIDNEY DISEASE. THIS IS A PRIMARY GLA MARIAL DISEASE WHICH HAS SCARRING IN THE KIDNEY ATTRIBUTEAL TO APOL1 AND THE GOAL WE HAVE BEEN ASPOUSING IS THESE VARIANTS INTERACT WITH ENVIRONMENTAL.

TRIGGERS TO CAUSE PROGRESSIVE KIDNEY DISEASE WITH SECONDARY HYPERTENSION. WE HAVE TO FIND THE ENVIRONMENTAL TRIGGERS TO LEAD TO THE CURIOUS. AND OUR NEW CONCEPT ABOUT APOL1 NEPHROPATHY IT’S NOT A INITIATOR OF KIDNEY DISEASE. IF YOU HAVE SICKLE CELL DISEASE, IF YOU HAVE HI INFECTION AND AREN’T NUCLEAR ANTIBODIES OR THESE PRIMARY VARIANTS WHERE WE DON’T KNOW WHAT THE SECOND HITS ARE YET, IN THE PRESENCE OF TWO RISK VARIANTS, KIDNEY DISEASE WILL PROGRESS. MILD KIDNEY DISEASE IN AFRICAN ANCESTRY AND POPULATIONBASED STUD CEASE WEAKLY ASSOCIATED. IT’S PROGRESSION. TO CONCLUDE, AFRICAN ANCESTRY.

ENRICHES FOR RISK VARIANTS FOR TYPE II DIABETES FOR NONDIABETIC FAMILY OF KIDNEY DISEASES AND FOR POOR RESPONSE TO HEPATITIS C PAPER THERAPY. EUROPEAN ANCESTRY ENRICHES FOR ARTHROSCLEROSIS, MI AND CALCIFIED PLAQUE. WE THINK LIKELY OSTEOPOROSIS IS A LINK TO VITAMIN D METABOLISM AND WHEN WE HAVE DONE ADD MIXTURE MAPPING, WE HAVE SEEN SIGNIFICANT DIFFERENCES IN AFRICAN AMERICANS WITH HIGH VERSUS LOW LEVELS. AND OF COURSE, IGA NEPHROPATHY ASSOCIATES WITH ASIAN AND EUROPEAN RISK AND RELATIVE PROTECTION IN AFTER CANS. THE PROBLEM IS, THAT SUBOPTIMAL HEALTH CARE ACCESS AND ENVIRONMENTAL EFFECT CAN REVERSE.

THESE GENETIC PREDICTORS. SO YOU DON’T SEE THE EUROPEAN RISK FOR ATH SCLEROSIS IN THE GENERAL POPULATION BECAUSE EUROPEAN HAVE BETTER ACCESS TO HEALTH CARE AND MY FINAL SLIDE, ALTHOUGH 99 OF THE GENOME IS SHARED AND WE ARE ALL FAR MORE ALIKE THAN DIFFERENT, THE REMAINING LESS THAN 1 CAN PRODUCE MARKED DIFFERENCES IN DISEASE SUSCEPTIBILITY AND TREATMENT. WE MUST CONSIDER THE EFFECTS OF ETHNICITY AND VARIANTS AND THE ENVIRONMENT TOGETHER TO UNDERSTAND THESE COMPLEX SOCIOAND GENETIC FACTORS. AND I’M ALWAYS AWARE THAT IN THE OLD DAYS WHEN I WAS PROPOSING.

HUMAN GENETIC STUDIES IN THE EARLY 90s, AND EVERY GRANT THAT WAS FUNDED WAS SOMEBODY’S ANIMAL MODEL OF HYPERTENSIVE NEVER SCLEROSIS BECAUSE IT BETTER MIMICKED HUMAN DISEASE, QUI DON’T EACH KNOW A GOOD MODEL OF HUMAN DISEASE BECAUSE APOL ONE NEPHROPATHY DOESN’T EXIST IN ANYBODY BUT AFRICAN ANCESTRY POPULATIONS. SO, WE MUST BE VERY CAREFUL WHAT WE TALK ABOUT AND THERE ARE ETHNICSPECIFIC VARIATIONS IN DISEASE RISK. SO I WANT TO THANK YOU ALL FOR THIS TREMENDOUS HONOR OF COMING HERE AND I WANTED TO THANK MY COLLEAGUES, DON BAUD EN, CARL.

LANG DISPELLED MY COLLABORATORS AT NIH FROM THE STUDIES AND DOCTORS KIMMEL AND ALL THE AGENCIES THAT FUNDED OUR WORK. THANK YOU. APPLAUSE gtgt WE HAVE TIME FOR QUESTIONS. THERE ARE MICROPHONES IN THE AISLE SO IS PEOPLE LISTENING ON THE WEB CAN HEAR THE QUESTIONS. LET ME AND YOU, IN TERMS OF CONTROVERSY ABOUT WHETHER IT’S A GOOD THING OR NOT TO POINT TO VARIATIONS BETWEEN POPULATIONS THAT MAY PLAY A ROLE IN DISEASE RISK, I THINK YOU WOULD AGREE THIS PROVIDES US WITH INSIGHTS IN THE APOL1 IS JUST ONE EXAMPLE.

OF PATHOGENESIS THAT WE MIGHT OTHERWISE NOT HAVE DISCOVERED. BUT ISN’T IT ALSO APPROPRIATE TO IMAGINE THAT ULTIMATELY, WE WOULD WANT TO GET AWAY FROM THE USE OF ETHNIC LABELS AS SLOPPY SURROGATES OF WHAT YOU’RE REALLY INTERESTED IN, WHICH IS THE INDIVIDUAL AND THE INDIVIDUAL’S GENETIC AND ENVIRONMENTAL MAKEUP gtgt ABSOLUTELY. SO WE LOOK AT EVERYBODY AS A MIXED BAG OF DIFFERENT ANCEST REESE AND WE CAN CALCULATE AND COMPUTE THAT FAIRLY WELL. THE THING THAT BOTHERS ME IS THAT WE USE A TERM LIKE, HYPERTENSIVE KIDNEY DISEASE EQUALLY IN AFRICAN AMERICAN.

POPULATIONS AND EUROPEAN AMERICAN POPULATIONS WHEN YOU TREAT HYPERTENSIVE CKD WITH KIDNEY PROBLEMS THAT IS WHITE, YOU CAN STOP THE KID FEE DISEASE IT WON’T PROGRESS. BUT IN AFRICAN AMERICANS IT WILL PROGRESS. THE LABELING OF THE DISEASE IS JUST AS IMPORTANT AS THE POPULATION, WE WANT TO GET TO THE GENOME LEVEL AND AS LONG AS THE DATA IS USED OBJECTIVELY, I DON’T WANT LIKE TO HEAR MEDICAL STUDENTS AND MEDICAL STUDENTS PRESENT A CASE AS A 60 YEARLY FEMALE. I WANT TO KNOW IF THEY ARE AFRICAN AMERICAN OR EUROPEAN.

AMERICAN. IT MAY NOT ALWAYS TRACK DIRECTLY WITH DISEASE BUT IT IS A LOT LESS EXPENSIVE THAN A CAT SCAN OR MRI. SO AS LONG AS YOU DON’T APPLY BIAS, I WANT TO KNOW ETHNICITY WHEN IT CAN INTERACT WITH DISEASE BUT I ALSO WANT TO KNOW THE REAL GENETICS SUSCEPTIBILITY THAT UNDERLIES IT. gtgt CONGRATULATIONS FOR A SEX EXCELLENT CLINICAL STUDY SHOWING SOME OF THE PARAMETERS IN THE CALCIUM LEVEL AS WELL AS KIDNEY DISEASE. IN THESE DAYS, WE HEAR THE LARGER USE OF VITAMIN D IN THE CANCER AND QUITE A FEW OTHER.

IDEAS THAT SHOW BENEFICIAL FROM 600 INTERNATIONAL UNITS TO ALMOST 1200 NOW. SO YOU MENTIONED ABOUT SOME VARIATIONS AND HOW DOES IT EFFECT PEOPLE LIKE US IN TERMS OF THIS VITAMIN D EFFECT ON THE CALCIUM LEVEL. gtgt I THINK THE QUESTION IS, WHAT ARE OUR TARGETS AS CLINICAL PHYSICIANS I DON’T THINK WE KNOW THE NORMAL RANGE OF VITAMIN D IN AFRICAN ANCESTRY POPULATIONS. I THINK THE KEY IS WE WANT TO KNOW THE BONE PHENOTYPE. WE WANT TO KNOW IF THEY ARE OSTEOPENIC OR OSTEOPROTTIC. WHETHER THEY ARE AFRICAN,.

EUROPEAN, ASIAN, I WANT TO KNOW IF THEY HAVE BONE DISEASE ON THE DEXA. IF THEY DO, THEN OF EUROPEAN ANCESTRY, THEY WILL RESPOND TO VITAMIN D. I DON’T THINK WE HAVE THE ANSWER FOR AFRICAN POPULATIONS YET AND MORE WORK NEEDS TO BE DONE BUT I WOULD CAUTION AGAINST WIDESPREAD SUPITATION WITHOUT BONE DISEASE BECAUSE WE DON’T KNOW WHAT IS DOES TO CORE NAY I R. NARY ARTERY CALCIUM AND IT WORSENS BONE DENSITY, WE THINK. gtgt THE STUDIES 17 AND I SEE SOME OF THE GENES FROM MARCH TO QUITE.

A FEW OTHER ONES THAT RELATES TO THIS TRANSFORMATION FROM SMOOTH MUSCLE CELLS. SO WHAT IS THE CELL INTO THE CORONARY ARTERY THAT IS RESPONSIBLE FOR THE CALLS CALCIFICATION AND WHAT ARE THE OTHER PARAMETER IN THE APPLAUSE THAT EFFECTS THAT. gtgt THE CELLS CHANGE TO A RETURNS PATHWAY AND GET ALL THE SIGNALING OF AN OSTEOBLAST BUT WE ARE STILL IN THE FINE MAPPING PHASE. I JUST WANTED TO MAKE THE POINTED THAT WITH ANCESTRY MAPPING, 11 OF 11 REGIONS THAT HAD DIFFERENT ETHNICITY WITH HIGH CORE NAY NARY CALCIUM WERE.

OF EUROPEAN ORANGE IN. THAT WAS THE ONLY POINT. WE ARE GOING TO FIND THOSE GENES IN THE COMING MONTHS, I HOPE. gtgt GOOD LUCK. WE NEED THIS STUDY. gtgt THAT WAS AN EXCELLENT PRESENTATION. THANK YOU VERY MUCH. AND IN FOLLOWUP, WE ARE STUDYING VITAMIN D LEVELS IN AFRICAN IMMIGRANTS TO THE UNITED STATES. AND I’D LIKE TO TELL YOU THAT WE JUST ANALYZED THE DATA YESTERDAY AND THAT 60 OF AFRICAN IMMIGRANTS TO THE UNITED STATES HAVE INSUFFICIENT VITAMIN D LEVELS ACCORDING TO IOM STANDARDS AND 90 HAVE LOW.

VITAMIN D LEVELS ACCORDING TO THE ENDOCRINE SOCIETY LEVELS. AND WE ARE GOING TO RELAY THAT TO BONE DISEASE IN DEXASCANS. gtgt THAT’S VERY INTERESTING. gtgt IT’S CRITICAL TO LINK THAT. A APPLAUD YOU. IT WILL BE EXCITING DADA. gtgt THANK YOU FOR GIVING THIS EXCELLENT TALK. I HAVE ONE FOLLOWUP QUESTION TO WHAT I DON’T KNOW WITH RESPECT TO AS FAR AS LOOKING AT A SMALL SUB SUBSET OF AFTER CANS WORLDWIDE, HAVE YOU LOOKED AT PURE AFRICAN POPULATIONS FROM THE CONTINENT AS WELL AS CARIBBEAN gtgt YES. gtgt EPIGENETIC PHENOMENON THAT IS.

REALLY THE MOST STRIKING PHENOMENON THAT YOU’RE SEEING gtgt THAT’S A GREAT QUESTION. WE HAVE NOT DONE THAT WORK BUT AFTER MY MEETING WITH Dr. REQUIEMY TODAY I’M OPTIMISTIC THESE TYPES OF COLLABORATIONS WILL DEVELOP. gtgt HE WILL 0 THE QUESTION HAVING COME TO THE MICROPHONE. gtgt IT’S AN EXCELLENT TALK. SO AS FULL DISCLOSURE, RICHARD COOPER IS MY MENTOR. SO I TRAINED FROM UNDER HIM. BUT THE POINTED I WANTED TO MAKE ALSO IS IS THAT FOLLOWING THE COMMENT FROM THE Dr. COLLINS, IT’S THAT YES, WE SEE THIS DIFFERENCE BUT IT’S NOT A.

CHARACTERISTIC OF THAT ETHNIC GROUP. BECAUSE AS YOU SHOWED, SOME TIMES IT’S 12 OF THAT GROUP THAT CARRY PARTICULAR VARIANT. SO WHEN CICI AFRICAN AMERICAN, OR AFRICAN SO WHEN WE SEE AFRICAN AMERICAN, WE START THAT DISTRIBUTION WE SEE. SO DEFINE THAT SOMETHING IS MORE FREQUENT DOESN’T DEFINE THAT POPULATION. I THINK THAT IS WHERE WE NEED TO BE, TO BE CAREFUL. gtgt I AGREE AND I THINK WE ARE TALKING ABOUT POPULATION GROUPS NOT REALLY ETHNICITIES AND RACES AND WE ARE ALL DIFFERENT MIXES OF OUR ANCESTOR’S VARIANTS. I AGREE FULLY AND IF MY TALK WAS.

TAKEN ANY OTHER WAY, I APOLOGIZE. gtgt LAST QUESTION. gtgt AND THE TERMS OF THE SECOND HITS THAT YOU LISTED FOR THE APOL1 EFFECT, AT LEAST TWO AS I I LOOK QUICKLY WERE SUSCEPTIBILITY OR PROTECTIVE AND MALARIA. AND I WONDERED IF THAT IS THE HEMOGLOBIN S AND SLE RISK FACTORS THAT ARE PROTECTED IN MALARIA IN SEVERE DISEASE AND WONDERING IF WHAT YOU’RE THINKING IN TERMS OF HOW THESE WERE SELECTED GIVEN APOL1 PROTECTIVE EFFECT ON IN SLEEPING SICKNESS ARE THEY ALL INTERACTING THE SAME WAY IN THOSE INFECTIOUS.

DISEASES INITIALLY gtgt I HAVE TO SAY WE HAVEN’T QUITE FIGURED THIS OUT YET. AND WITH THE ANTINUCLEAR ANTIBODIES I WASN’T AWARE THAT PROTECTED FROM MA LARIAL INFECTION. APOL 1 IS NOT ASSOCIATED WITH MILD LINE UP US NEVERRITIS. WE LOOKED AT THIS WITH JEFFREY KOPP AND SAMPLES HERE AND WE DIDN’T SEE AN ASSOCIATION WITH JUST MILD LUPUS NEVERRITIS THAT RESPONDED TO THERAPY. YOU NEED PROGRESSORS ALL THE WAY TO DIALYSIS. SO I DON’T HAVE THE ANSWERS TO HOW THOSE FACTORS INTERACT YET. BUT WE ARE MOST INTERESTED IN OTHER VIRUSES NONHIV VIRAL.

48 Nerve Damage Morphine Addiction Gone Faster EFT

The most amazing thing I’ve ever had happen in my life and really we all have amazing things but the this is a situation that I have been dealing with, and dealing with it very terrible pain that occurred from a happening in my life where, what was it Sherrie 1998 They damaged that major nerve. 1998 I end up going in for a angiogram, after being treated by physician for in ear infection and I went in a hospital in Orlando. If you guys are ever in Orlando and you need to go to hospital, that’s a topflight.

Place. We were very blessed that they come up with what they call a crises radiologist, but they discovered that I had a a blood clot in my right vertebral artery and they had to go back up my groin and bust the blood clot, then they went back up it again in put in a stent, due to the condition of the right vertebral artery. The left one was gone and it’s just something that happens to people. but anyway I was just sitting there and, just feeling this awful knot in my groin and.

Since this happened. they have, invaded my brain like 12 or 13 times, so if I say something crazy, or I’m doing something crazy you understand, It is a situation from having your brain invaded and it has made a big difference by Robert very capably set me down and we went through the tapping method. and. hey folks I’m not I’m not lying to you, Robert quit and he says How’s the pain and it’s gone! And this is after four or five years. I was treated oneyear, a couple years ago, for.

I was on morphine and spent a month in the hospital trying to get off of it. And now my groin, the pain has gone the burning has gone and I haven’t smoked a cigarette since last Tuesday afternoon about 2 o’clock! I’ve never been happier in my life and I feel like, thanks to our friend here, he was very capable, I was very much at ease with him and I feel very fortunate, very blessed to have crossed paths with with Robert. Thank you. I’ve watched Paul and his suffering and we almost lost him a couple years ago.

Because the morphine that they were giving him had shut down his system his colon and he was severely obstructed and then they put him on this patch that is, I guess, very addictive and the VA Veterans Administration doctors are just he got special permission to to use the patch, because they said once this nerve is damaged it cannot be repaired, it will not heal itself. And yet he’s pain free now! He’s suffered from a terrific amount of burning and it’s just been a miracle, an absolute miracle.

The Effect Of Fructose On Diabetics

Hello today and welcome to another tutorial, today we are going to speak about the effect of fructose on diabetics,first of all lets start by the definition of diabetes.Diabetes is a metabolic disorder that causes a lack of absorption of sugar in the blood due to the lack of insulin, insulin acts as a straw it allows glucose to get into the cells but in case of diabetes not producing any insulin or insulin resistant. Many of us know that diabetes has been there for millennia, it was an obscure disease that no one knew how.

To deal with, but it was not until the 20th century when modern medicine appeared that life saving treatments was developed like synthetic insulin shots and oral medication, since then diabetes was more of a controllable disease. But how can we control it And is fructose a threat on diabetics this is the question we are going to answer today. Let’s start by the meaning of fructose, it is simply a type of sugar found in fruits and honey, it is known for how easily it can be digested and absorbed by the body. And in fact many studies have shown that it’s.

An important agent to control blood sugar with diabetics, according to the university of Minnesota fructose should be included in the diabetic’s diet, in this research we tested type 2 diabetics before and after ingesting a 100 grams piece of fruit in the breakfast time without having any medications for at least 4 hours, we used fruits like bananas, apples, oranges, pineapples and pears. We tested the diabetics daily for five consecutive days with one fruit each day. The results have shown that type 2 diabetics experienced fluctuating blood glucose level , for instance , bananas decreased their blood sugar by 15.

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