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A large-scale association analysis of common variation of the HNF1α gene with type 2 diabetes in the U.K. Caucasian population

Lookup NU author(s): Professor Mark Walker


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HNF1α (TCF1) is a key transcription factor that is essential for pancreatic β-cell development and function. Rare mutations of HNF1α cause maturity-onset diabetes of the young. A common variant, G319S, private to the Oji-Cree population, predisposes to type 2 diabetes, but the role of common HNF1α variation in European populations has not been comprehensively assessed. We determined the linkage disequilibrium and haplotype structure across the HNF1α gene region using 29 single nucleotide polymorphisms (SNPs). Eight tagging SNPs (tSNPs) that efficiently capture common haplotypes and the amino acid- changing variant, A98V, were genotyped in 5,307 subjects (2,010 type 2 diabetic case subjects, 1,643 control subjects, and 1,654 members of 521 families). We did not find any evidence of association between the tSNPs or haplotypes and type 2 diabetes. We could exclude odds ratios (ORs) >1.25 for all tSNPs. The rare V98 allele (∼3% frequency) showed possible evidence of association with type 2 diabetes (OR 1.23 [95% CI 0.99-1.54], P = 0.07), a result that was supported by meta-analysis of this and published studies (OR 1.31 [1.08-1.59], P = 0.007). Further studies are required to investigate this association, demonstrating the difficulty of defining the role of rare (<5%) alleles in type 2 diabetes risk. © 2005 by the American Diabetes Association.

Publication metadata

Author(s): Weedon MN, Owen KR, Shields B, Hitman G, Walker M, McCarthy MI, Hattersley AT, Frayling TM

Publication type: Article

Publication status: Published

Journal: Diabetes

Year: 2005

Volume: 54

Issue: 8

Pages: 2487-2491

Print publication date: 01/08/2005

ISSN (print): 0012-1797

ISSN (electronic): 1939-327X

Publisher: American Diabetes Association


DOI: 10.2337/diabetes.54.8.2487

PubMed id: 16046319


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