Upstream transcription factor 1 (USF1) in risk of type 2 diabetes: Association study in 2000 Dutch Caucasians

S.J. Meex, J.V. van Vliet-Ostaptchouk, C.J.H. van der Kallen, M.M.J. van Greevenbroek, C.G. Schalkwijk, E.J.M. Feskens, E.E. Blaak, C. Wijmenga, M.H. Hofker, C.D. Stehouwer, T.W. de Bruin

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Abstract

Type 2 diabetes shares substantial genetic and phenotypic overlap with familial combined hyperlipidemia. Upstream stimulatory factor 1 (USF1), a well-established susceptibility gene for familial combined hyperlipidemia, is postulated to be such a shared genetic determinant. We evaluated two established variants in familial combined hyperlipidemia (rs2073658 and rs3737787) for association with type 2 diabetes in two Dutch case-control samples (N=2011). The first case-control sample comprised 501 subjects with type 2 diabetes from the Breda cohort and 920 healthy blood bank donors of Dutch Caucasian origin. The second case-control sample included 211 subjects with type 2 diabetes, and 379 normoglycemic controls. SNP rs2073658 and SNP rs3737787 were in perfect linkage disequilibrium. In the first case-control sample, prevalence of the major allele was higher in patients than in controls (75% versus 71%, OR=1.25, p=0.018). A similar effect-size and -direction was observed in the second case-control sample (76% versus 72%, OR=1.22, p=0.16). A combined analysis strengthened the evidence for association (OR=1.23, p=0.006). Notably, the increased risk for type 2 diabetes could be ascribed to the major allele, and its high frequency translated to a substantial population attributable risk of 14.5%. In conclusion, the major allele of rs2073658 in the USF1 gene is associated with a modestly increased risk to develop type 2 diabetes in Dutch Caucasians, with considerable impact at the population level. AD - University of Maastricht, Cardiovascular Research Institute Maastricht (CARIM), Department of Internal Medicine, Division of General Internal Medicine, Laboratory for Metabolism and Vascular Medicine, P.O. Box 616, 6200MD Maastricht, The Netherlands.
Original languageEnglish
Pages (from-to)352-355
JournalMolecular Genetics and Metabolism
Volume94
Issue number3
DOIs
Publication statusPublished - 1 Jan 2008

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