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

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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. © 2008 Elsevier Inc. All rights reserved.

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Meex, S. J. R., van Vliet-Ostaptchouk, J. V., van der Kallen, C. J. H., van Greevenbroek, M. M. J., Schalkwijk, C. G., Feskens, E. J. M., … de Bruin, T. W. A. (2008). Upstream transcription factor 1 (USF1) in risk of type 2 diabetes: Association study in 2000 Dutch Caucasians. Molecular Genetics and Metabolism, 94(3), 352–355. https://doi.org/10.1016/j.ymgme.2008.03.011

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