Hepatocyte nuclear factor-4alpha P2 promoter haplotypes are associated with type 2 diabetes in the Japanese population.

Diabetes
Kazuo HaraTakashi Kadowaki

Abstract

Hepatocyte nuclear factor (HNF)-4alpha is a transcription factor known as a key molecule in the development and functions of the beta-cells. In a previously performed genome-wide scan of Japanese type 2 diabetic sibpairs, we observed linkage of type 2 diabetes to chromosome 20q12-q13, a region in which the HNF4A gene is located. Recent studies have reported associations between type 2 diabetes and polymorphisms in the P2 promoter region specific to beta-cells. In this study, we attempted to assess whether the HNF4A gene plays a role in the genetic susceptibility to type 2 diabetes in the Japanese population by analyzing polymorphisms and haplotypes of the HNF4A gene. Linkage disequilibrium across the P2 promoter region was preserved in the Japanese population, consistent with previous reports. Although none of the individual polymorphisms examined showed any significant association with type 2 diabetes, we found very strong evidence of the association between type 2 diabetes and the haplotype consisting of two polymorphisms in the P2 promoter region of the HNF4A gene (P = 3.82 x 10(-4)). In contrast, there was no association between type 2 diabetes and haplotypes consisting of polymorphisms not located in the P2 promoter region...Continue Reading

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Citations

Apr 12, 2007·Current Diabetes Reports·Michael N Weedon, Timothy M Frayling
Jun 15, 2007·Current Opinion in Clinical Nutrition and Metabolic Care·Latisha Love-Gregory, M Alan Permutt
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Oct 18, 2007·Current Opinion in Endocrinology, Diabetes, and Obesity
Oct 18, 2007·Current Opinion in Endocrinology, Diabetes, and Obesity

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