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Leif Groop

Leif Groop

Principal investigator

Leif Groop

Association testing of variants in the hepatocyte nuclear factor 4 alpha gene with risk of type 2 diabetes in 7,883 people

Author

  • W Winckler
  • R R Graham
  • P I W de Bakker
  • M Sun
  • Peter Almgren
  • T Tuomi
  • D Gaudet
  • T J Hudson
  • K G Ardlie
  • M J Daly
  • J N Hirschhorn
  • Leif Groop
  • D Altshuler

Summary, in English

Two recent publications reported association of common polymorphisms in the P2 promoter of hepatocyte nuclear factor 4alpha (HNF4alpha) (the MODY1 gene) with risk for type 2 diabetes. We attempted to reproduce this putative association by genotyping 11 single nucleotide polymorphism (SNPs) spanning the HNF4a coding region and the P2 promoter in >3,400 patients and control subjects from Sweden, Finland, and Canada. One SNP that was consistently associated in the two previous reports (rs1884613, in the P2 promoter region) also trended in the same direction in our sample, albeit with a lower estimated odds ratio (OR) of 1.11 (P = 0.05, one-tailed). We genotyped this SNP (rs1884613) in an additional 4,400 subjects from North America and Poland. In this sample, the association was not confirmed and trended in the opposite direction (OR 0.88). Meta-analysis of our combined sample of 7,883 people (three times larger than the two initial reports combined) yielded an OR of 0.97 (P = 0.27). Finally, we provide an updated analysis of haplotype structure in the region to guide any further investigation of common variation in HNF4alpha. Although our combined results fail to replicate the previously reported association of common variants in HNF4alpha with risk for type 2 diabetes, we cannot exclude an effect smaller than that originally proposed, heterogeneity among samples, variation in as-yet-unmeasured genotypic or environmental modifiers, or true association secondary to linkage disequilibrium (LD) with as-yet-undiscovered variant(s) in the region.

Department/s

  • Genomics, Diabetes and Endocrinology

Publishing year

2005

Language

English

Pages

886-892

Publication/Series

Diabetes

Volume

54

Issue

3

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1939-327X