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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Epidemiology and Disease Control Subcommittee 2 (EDC)
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University of Texas Health Science Center San Antonio
Schools of Medicine
San Antonio
United States
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Farook, V S; Reddivari, L; Chittoor, G et al. (2015) Metabolites as novel biomarkers for childhood obesity-related traits in Mexican-American children. Pediatr Obes 10:320-7
SIGMA Type 2 Diabetes Consortium; Williams, Amy L; Jacobs, Suzanne B R et al. (2014) Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico. Nature 506:97-101
Chittoor, G; Farook, V S; Puppala, S et al. (2013) Localization of a major susceptibility locus influencing preterm birth. Mol Hum Reprod 19:687-96
Farook, Vidya S; Coletta, Dawn K; Puppala, Sobha et al. (2013) Linkage of type 2 diabetes on chromosome 9p24 in Mexican Americans: additional evidence from the Veterans Administration Genetic Epidemiology Study (VAGES). Hum Hered 76:36-46
Fowler, Sharon P; Puppala, Sobha; Arya, Rector et al. (2013) Genetic epidemiology of cardiometabolic risk factors and their clustering patterns in Mexican American children and adolescents: the SAFARI Study. Hum Genet 132:1059-71
Farook, Vidya S; Puppala, Sobha; Schneider, Jennifer et al. (2012) Metabolic syndrome is linked to chromosome 7q21 and associated with genetic variants in CD36 and GNAT3 in Mexican Americans. Obesity (Silver Spring) 20:2083-92
Thameem, Farook; Puppala, Sobha; Schneider, Jennifer et al. (2012) The Gly(972)Arg variant of human IRS1 gene is associated with variation in glomerular filtration rate likely through impaired insulin receptor signaling. Diabetes 61:2385-93
Thameem, Farook; Puppala, Sobha; Arar, Nedal H et al. (2011) Genetic variants in transient receptor potential cation channel, subfamily M 1 (TRPM1) and their risk of albuminuria-related traits in Mexican Americans. Clin Chim Acta 412:2058-62
Puppala, Sobha; Coletta, Dawn K; Schneider, Jennifer et al. (2011) Genome-wide linkage screen for systolic blood pressure in the Veterans Administration Genetic Epidemiology Study (VAGES) of Mexican-Americans and confirmation of a major susceptibility locus on chromosome 6q14.1. Hum Hered 71:1-10
Thameem, Farook; Puppala, Sobha; Lehman, Donna M et al. (2010) The Ser(326)Cys polymorphism of 8-oxoguanine glycosylase 1 (OGG1) is associated with type 2 diabetes in Mexican Americans. Hum Hered 70:97-101

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