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Diabetes 54:3035-3039, 2005
© 2005 by the American Diabetes Association, Inc.

Brief Genetics Reports

Variants in Hepatocyte Nuclear Factor 4{alpha} Are Modestly Associated With Type 2 Diabetes in Pima Indians

Yunhua Li Muller1, Aniello M. Infante1, Robert L. Hanson1, Latisha Love-Gregory2, William Knowler1, Clifton Bogardus1, and Leslie J. Baier1

1 Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Phoenix, Arizona
2 Washington University School of Medicine, St. Louis, Missouri

Single nucleotide polymorphisms (SNPs) within the hepatocyte nuclear factor 4{alpha} (HNF4{alpha}) gene are associated with type 2 diabetes in Finns and Ashkenazi Jews. Previous studies in both populations have reported linkage to type 2 diabetes near the HNF4{alpha} locus on chromosome 20q12-13. To investigate whether HNF4{alpha} is a diabetes susceptibility gene in Pima Indians, a population with the highest reported prevalence of type 2 diabetes but with no evidence for linkage of the disease on chromosome 20q, 19 SNPs across the promoter and coding region of HNF4{alpha} were genotyped for association analysis. In a group of 1,037 Pima Indians (573 diabetic and 464 nondiabetic subjects), three SNPs in HNF4{alpha} (rs3212183 and rs2071197 located in introns 3 and 1, respectively, and rs6031558, an extremely rare SNP located in the P2 promoter region) were modestly associated with type 2 diabetes (rs3212183 odds ratio [OR] 1.34 [95% CI 1.07–1.67], P = 0.009; rs2071197 1.34 [1.07–1.66], P = 0.008; and rs6031558 3.18 [1.03–9.84], P = 0.04, adjusted for age, sex, birth year, heritage, and family membership). We conclude that variants in HNF4{alpha} do not appear to be major determinants for type 2 diabetes in Pima Indians; however, HNF4{alpha} may have a minor role in type 2 diabetes susceptibility within this Native American population.

Address correspondence and reprint requests to Leslie Baier, PhD, Clinical Diabetes and Nutrition Section, NIDDK, NIH, 4212 N. 16th St., Phoenix, AZ 85016. E-mail: lbaier{at}phx.niddk.nih.gov

Abbreviations: FUSION, Finnish-U.S. Investigation of Type 2 Diabetes; HNF4{alpha}, hepatocyte nuclear factor 4{alpha}; SNP, single nucleotide polymorphism


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Copyright © 2005 by the American Diabetes Association.