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

作者：Meex Steven J R^*; van Vliet Ostaptchouk Jana V; van der Kallen Carla J H; van Greevenbroek Marleen M J; Schalkwijk Casper G; Feskens Edith J M; Blaak Ellen E; Wijmenga Cisca; Hofker Marten H; Stehouwer Coen D A; de Bruin Tjerk W A

来源：Molecular Genetics and Metabolism, 2008, 94(3): 352-355.

DOI：10.1016/j.ymgme.2008.03.011

• genetic association study
• single nucleotide polymorphism
• familial combined hyperlipidemia
• complex genetic diseases
• type 2 diabetes
• insulin resistance

Type 2 diabetes shares substantial genetic and phenotypic overlap with familial combined hyperlipidemia. Upstream stimulatory factor 1 (USF7), 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.

• 出版日期2008-7