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Lookup NU author(s): Professor Mark Walker
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OBJECTIVE-Single nucleotide polymorphisms (SNPs) in the P2 promoter region of HNF4A were originally shown to be associated with predisposition for type 2 diabetes in Finnish, Ashkenazi, and, more recently, Scandinavian populations, but they generated conflicting results in additional populations. We aimed to investigate whether data from a large-scale mapping approach would replicate this association in novel Ashkenazi samples and in U.K. populations and whether these data would allow us to refine the association signal. RESEARCH DESIGN AND METHODS-Using a dense linkage disequilibrium map of 20q we selected SNPs from a 10-Mb interval centered on HNF4A. In a staged approach, we first typed 4,608 SNPs in case-control populations from four U.K. populations and an Ashkenazi population (n = 2,516). In phase 2, a subset of 763 SNPs was genotyped in 2,513 additional samples from the same populations. RESULTS-Combined analysis of both phases demonstrated association between HNF4A P2 SNPs (rs1884613 and rs2144908) and type 2 diabetes in the Ashkenazim (n = 991; P 0.5), and the estimate for the OR was much smaller (OR 1.04; [95%CI 0.91-1.19]). CONCLUSIONS-These data indicate that the risk conferred by HNF4A P2 is significantly different between U.K. and Ashkenazi populations (P
Author(s): Barroso I, Luan JA, Wheeler E, Whittaker P, Wasson J, Zeggini E, Weedon MN, Hunt S, Venkatesh R, Frayling TM, Delgado M, Neuman RJ, Zhao JH, Sherva R, Glaser B, Walker M, Hitman G, McCarthy MI, Hattersley AT, Permutt MA, Wareham NJ, Deloukas P
Publication type: Article
Publication status: Published
Journal: Diabetes
Year: 2008
Volume: 57
Issue: 11
Pages: 3161-3165
ISSN (print): 0012-1797
ISSN (electronic): 1939-327X
Publisher: American Diabetes Association
URL: http://dx.doi.org/10.2337/db08-0719
DOI: 10.2337/db08-0719
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