The proposed research is a genetic epidemiologic study of non-insulin dependent diabetes mellitus (NIDDM) in families of randomly selected diabetic Mexican Americans, a high risk population for diabetes. A strong genetic component in NIDDM has long been recognized, although no clear pattern has yet been identified. Recent studies have suggested that insulin resistance may also be an inherited trait. The investigators propose to conduct pedigree studies to examine the relationship between NIDDM and four candidate genes affecting glucose metabolism (two glucose transporter genes (GLUT1 and GLUT4), the insulin receptor gene (INSR), and Amylin, a new candidate gene) and two marker phenotypes found previously to be associated with NIDDM in population studies (Rh blood group and haptoglobin). Approximately 720 individuals from 60 families will be studied over 5 years. Probands will be randomly selected from among all diabetic Mexican Americans identified in the San Antonio Heart Study, a population-based study of cardiovascular disease and diabetes. Subjects will receive a clinical examination during which fasting and two-hour levels of glucose, insulin, and C-peptides will be determined and anthropometric measurements will be obtained. Diabetes will be diagnosed according to World Health Organization criteria. Blood samples will also be drawn for analysis of DNA polymorphisms at the candidate gene loci. Lymphocytes from all participants will be transformed with Epstein-Barr virus and used to create a DNA bank as a future resource. Complex segregation analysis will be used to determine whether major genes influence the inheritance of NIDDM or serum glucose, insulin, and C-peptide levels. Quantitative trait linkage analysis will be used to determine whether any major genes identified in the segregation analyses are linked with polymorphisms of the candidate genes.
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