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- Title
Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population.
- Authors
Weedon, Michael N.; Owen, Katharine R.; Shields, Beverley; Hitman, Graham; Walker, Mark; McCarthy, Mark I.; Love-Gregory, Latisha D.; Permutt, M. Alan; Hattersley, Andrew T.; Frayling, Timothy M.
- Abstract
Hepatocyte nuclear factor (HNF)-4alpha is part of a transcription factor network that is key for the development and function of the beta-cell. Rare mutations in the HNF4alpha gene cause maturity-onset diabetes of the young. A number of type 2 diabetes linkage studies have found evidence of linkage to 20q12-13.1 where the HNF4alpha gene is located. Two recent studies have found an association between four common variants of the alternative P2 promoter region and type 2 diabetes. These variants are in strong linkage disequilibrium, and the minor alleles define one common risk haplotype. In both studies, the risk haplotype explained a large proportion of the evidence of linkage to 20q12-13.1. We aimed to assess this haplotype in a U.K. Caucasian study of 5,256 subjects. We typed two single nucleotide polymorphisms tagging the risk haplotype (rs4810424 and rs2144908) and found evidence of association in both case-control and family-based studies; rs4810424 marginally demonstrated the stronger association with an overall estimated odds ratio of 1.15 (95% CI 1.02-1.33) (P = 0.02). The effect of the P2 haplotype on type 2 diabetes risk is less than in the initial studies, probably reflecting that these studies used 20q12-13.1-linked cases. In conclusion, we have replicated the association of the HNF4alpha P2 promoter haplotype with type 2 diabetes in a U.K. Caucasian population where there is no evidence of linkage to 20q.
- Subjects
HEPATOCYTE growth factor; TRANSCRIPTION factors; PANCREATIC beta cells; DIABETES; GENES
- Publication
Diabetes, 2004, Vol 53, Issue 11, p3002
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.53.11.3002