Structural Analysis Of Genes For Type 2 Diabetes &Obesi

Baier, Leslie J.

Abstract

A gene is considered a candidate gene for type 2 diabetes in Pima Indians if 1) it has a known physiological function in a pathway relevant to type 2 diabetes/obesity or 2) it is associated with diabetes/obesity in another human population or in an animal model. Candidate genes analyzed in the past year include: MCR4, FAS, PYY, Y2R, HNF4alpha, SUR, KIR6.2, LEPR, LEP, POMC, GRL, NPY, ADRB3, MC3R, GHRL and AGRP. Poymorphisms were identified in all of these genes and analyzed for association with type 2 diabetes, obesity, or metabolic traits that predict these diseases. Although none of these genes appear to have a significant role in determining type 2 diabetes or obsity in Pima Indians, we did observe some minor associations. For example, multiple variants in the HNF4alpha gene have ben reported to be associated with type 2 diabetes in a Finnish study population and the Ashkenazi Jewish population. Analysis of these variants in Pima Indians identified one variant that was also associated with type 2 diabetes, and two additional variants were associated wth insulin resitance, in this Native American population. In addition, analysis of the PYY and Y2R genes identified modest associations between genetic variations and severe obesity in male Pima Indians.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Type: Intramural Research (Z01)
• Project #: 1Z01DK069071-08
• Application #: 6984165
• Study Section: (PECR)
• Support Year: 8
• Fiscal Year: 2004

Institution

• Name: U.S. National Inst Diabetes/Digst/Kidney
• Country: United States

Publications

Traurig, Michael; Mack, Janel; Hanson, Robert L et al. (2009) Common variation in SIM1 is reproducibly associated with BMI in Pima Indians. Diabetes 58:1682-9

Rong, Rong; Hanson, Robert L; Ortiz, Daniel et al. (2009) Association analysis of variation in/near FTO, CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, LOC387761, and CDKN2B with type 2 diabetes and related quantitative traits in Pima Indians. Diabetes 58:478-88

Traurig, M; Hanson, R L; Kobes, S et al. (2007) Protein tyrosine phosphatase 1B is not a major susceptibility gene for type 2 diabetes mellitus or obesity among Pima Indians. Diabetologia 50:985-9

Guo, Tingwei; Hanson, Robert L; Traurig, Michael et al. (2007) TCF7L2 is not a major susceptibility gene for type 2 diabetes in Pima Indians: analysis of 3,501 individuals. Diabetes 56:3082-8

Korner, A; Ma, L; Franks, P W et al. (2007) Sex-specific effect of the Val1483Ile polymorphism in the fatty acid synthase gene (FAS) on body mass index and lipid profile in Caucasian children. Int J Obes (Lond) 31:353-8

Traurig, Michael T; Permana, Paska A; Nair, Saraswathy et al. (2006) Differential expression of matrix metalloproteinase 3 (MMP3) in preadipocytes/stromal vascular cells from nonobese nondiabetic versus obese nondiabetic Pima Indians. Diabetes 55:3160-5

Guo, Yan; Traurig, Michael; Ma, Lijun et al. (2006) CHRM3 gene variation is associated with decreased acute insulin secretion and increased risk for early-onset type 2 diabetes in Pima Indians. Diabetes 55:3625-9

Muller, Yunhua Li; Infante, Aniello M; Hanson, Robert L et al. (2005) Variants in hepatocyte nuclear factor 4alpha are modestly associated with type 2 diabetes in Pima Indians. Diabetes 54:3035-9

Kovacs, P; Ma, L; Hanson, R L et al. (2005) Genetic variation in UCP2 (uncoupling protein-2) is associated with energy metabolism in Pima Indians. Diabetologia 48:2292-5

Ma, Lijun; Tataranni, P Antonio; Hanson, Robert L et al. (2005) Variations in peptide YY and Y2 receptor genes are associated with severe obesity in Pima Indian men. Diabetes 54:1598-602