title: Upstream transcription factor 1 (USF1) in risk of type 2 diabetes: association study in 2000 Dutch Caucasians.
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.
authors.affiliation: University of Maastricht, Cardiovascular Research Institute Maastricht (CARIM), Department of Internal Medicine, Maastricht, The Netherlands. steven.meex@intmed.unimaas.nl
authors.forename: Steven J R
authors.initials: SJ
authors.lastname: Meex
authors.forename: Jana V
authors.initials: JV
authors.lastname: van Vliet-Ostaptchouk
authors.forename: Carla J H
authors.initials: CJ
authors.lastname: van der Kallen
authors.forename: Marleen M J
authors.initials: MM
authors.lastname: van Greevenbroek
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: Edith J M
authors.initials: EJ
authors.lastname: Feskens
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Marten H
authors.initials: MH
authors.lastname: Hofker
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: Tjerk W A
authors.initials: TW
authors.lastname: de Bruin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D051720:Upstream Stimulatory Factors / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors