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. 2005 Oct;54(10):3035-9.
doi: 10.2337/diabetes.54.10.3035.

Variants in hepatocyte nuclear factor 4alpha are modestly associated with type 2 diabetes in Pima Indians

Yunhua Li Muller  1 , Aniello M Infante, Robert L Hanson, Latisha Love-Gregory, William Knowler, Clifton Bogardus, Leslie J Baier
Affiliations

Variants in hepatocyte nuclear factor 4alpha are modestly associated with type 2 diabetes in Pima Indians

Yunhua Li Muller et al. Diabetes. 2005 Oct.

Abstract

Single nucleotide polymorphisms (SNPs) within the hepatocyte nuclear factor 4alpha (HNF4alpha) 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 HNF4alpha locus on chromosome 20q12-13. To investigate whether HNF4alpha 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 HNF4alpha were genotyped for association analysis. In a group of 1,037 Pima Indians (573 diabetic and 464 nondiabetic subjects), three SNPs in HNF4alpha (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 HNF4alpha do not appear to be major determinants for type 2 diabetes in Pima Indians; however, HNF4alpha may have a minor role in type 2 diabetes susceptibility within this Native American population.

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Figures

FIG. 1
FIG. 1
Relative positions of 21 SNPs within the HNF4α locus selected for analysis in Pima Indians. ○, SNPs analyzed for type 2 diabetes in Pima Indians and either Finns or Ashkenazi Jews (or both); □, SNPs analyzed for type 2 diabetes in Pima Indians only; •, SNP (rs3212183) associated with type 2 diabetes in both Pima Indians and Finns; ▪, SNPs (rs2071197 and rs6031558) associated with type 2 diabetes in Pima Indians not typed in other populations. rs2144908* is in complete genotypic concordance with rs1884614; rs6031552* is in complete genotypic concordance with rs6031558.
FIG. 2
FIG. 2
Pairwise linkage disequilibrium among SNPs in the HNF4α region in Pima Indians. Values in the upper right represent D′, while values in the bottom left represent Δ2. Genotypes of 19 SNPs from 1,037 individuals typed for the diabetes association analysis were used to determine the pairwise linkage disequilibrium.
See this image and copyright information in PMC

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