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PROJECT SUGAR Genetic and Metabolic Basis of Diabetes and Obesity in Gullah-Speaking African Americans

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PROJECT SUGAR Genetic and Metabolic Basis of Diabetes and Obesity in Gullah-Speaking African Americans

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    1. PROJECT SUGAR Genetic and Metabolic Basis of Diabetes and Obesity in Gullah-Speaking African Americans W. Timothy Garvey, MD Department of Nutrition Sciences University of Alabama at Birmingham

    2. Causes of Hyperglycemia in Type 2 Diabetes

    3. Variation in Insulin Sensitivity

    4. Metabolic Syndrome Insulin Resistance Syndrome, Syndrome X Hyperinsulinemia Impaired glucose tolerance Obesity Increased visceral fat distribution Hypertriglyceridemia/ Low HDL Small, dense LDL Hypertension Positive family history Disfibrinolysis (high PAI-1) Vascular reactivity/ endothelial dysfunction Inflammation Microalbuminuria Polycystic ovary syndrome NAFLD

    5. Secreted Adipocyte Factors

    7. Multiple Criteria for Metabolic Syndrome

    13. Coastal Africa showing historical areas of rice culture Rice had been in cultivation in Africa, and particularly in Sierra Leone, for centuries before the trans-Atlantic slave trade began. Thus, Sierra Leone became a significant slave exportation site, especially for slaves bound for South Carolina rice plantations. Though today�s overall African American population is an admixed population of, primarily, African and Caucasian populations, numerous cultural, linguistic, culinary, and historical studies have demonstrated closer associations between the current Gullah and Sierra Leone populations than between between other African Americans and African populations. Rice had been in cultivation in Africa, and particularly in Sierra Leone, for centuries before the trans-Atlantic slave trade began. Thus, Sierra Leone became a significant slave exportation site, especially for slaves bound for South Carolina rice plantations. Though today�s overall African American population is an admixed population of, primarily, African and Caucasian populations, numerous cultural, linguistic, culinary, and historical studies have demonstrated closer associations between the current Gullah and Sierra Leone populations than between between other African Americans and African populations.

    14. Links between Gullahs and �Rice Coast� of West Africa Colonists need rice growing expertise Historical record Language: Gullah � Krio Cultural similarities Genetic studies

    15. Advantages for Genetic Studies in the Gullahs Minimal genetic admixture Geographical isolation and cultural identity Large stable multi-generational families High prevalence and relative risk for T2DM, obesity, hypertension, lupus, prostate cancer Uniform diet and lifestyle (maximize expression of disease in patients with susceptibility genes)

    16. Admixture Estimates in African American Populations: Autosomal Markers

    17. As expected, Caucasians are consistently more genetically distant from all other populations for each genetic distance model studied. No other consistent interpretation across all samples follows from these trees, but the Gullah and Sierra Leone samples are generally close across each genetic distance model. The represented distance between Sierra Leone and each of Jamaican, Charleston African American, and west coast African American samples varies across the models. As expected, Caucasians are consistently more genetically distant from all other populations for each genetic distance model studied. No other consistent interpretation across all samples follows from these trees, but the Gullah and Sierra Leone samples are generally close across each genetic distance model. The represented distance between Sierra Leone and each of Jamaican, Charleston African American, and west coast African American samples varies across the models.

    19. Project Sugar Objectives SCIENCE Ascertain sib-pairs and pedigrees with T2DM, Obesity Phenotype: anthropometrics, glucose tolerance, lipids, blood pressure, health beliefs/practices Study genes contributing to T2DM and Obesity in a homogeneous African-derived population: whole genome scan, candidate genes SERVICE Health education, disease screenings, health fairs, referrals

    21. COMMUNITY Research Coupled with Community Service, Education, and Participation

    23. Insulin Resistance Trait Cluster in Gullah-speaking African Americans

    25. Multiple Criteria for Metabolic Syndrome

    27. Mitochondrion

    31. UCP3 exon 6 splice variant affects macronutrient fuel partitioning

    32. UCP3 Exon 6 Splice-Donor Variant is Associated with Severe Obesity

    33. Project Sugar Whole genome scan for Diabetes/Obesity Genes in Gullah-Speaking African Americans Key phenotypes: Type 2 Diabetes, BMI, NMR lipoprotein subclass profile DNA submitted to CIDR 1028 Represent 426 families (2-7 members) Affected sib-pair study design with T2DM 834, Unaffected 194 CIDR recently completes Panel IV Illumina SNP scan = ~6,000 SNPs Statistical Genetics: Michele Sale (UVa) and Carl Langefeld (WFU)

    34. Chromosome 3 Linkages for Diabetes With and Without Regard to Age of Onset

    43. Metabolic Evolution of Type 2 Diabetes

    46. Linkages for Waist Circumference in Gullah Speaking Americans

    47. The correlation between HMW Adiponectin and components of the metabolic syndrome varies by ethnicity

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