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

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

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Scopus)

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%.
Original languageEnglish
Pages (from-to)352-355
JournalMolecular Genetics and Metabolism
Volume94
Issue number3
DOIs
Publication statusPublished - 2008

Keywords

  • familial combined hyperlipidemia
  • genome-wide scan
  • provides independent replication
  • stimulatory factor-1
  • susceptibility locus
  • chromosome 1q21-q24
  • metabolic syndrome
  • glucose-intolerance
  • gene-gene
  • linkage

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