Risk of ischemic vascular disease in 52 000 individuals

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Original Article

The Pharmacogenomics Journal advance online publication 4 August 2009; doi: 10.1038/tpj.2009.34

Common polymorphisms in CYP2C9, subclinical atherosclerosis and risk of ischemic vascular disease in 52 000 individuals

D Kaur-Knudsen1,2,4, S E Bojesen1,2,3,4 and B G Nordestgaard1,2,3,4

1. Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark
2. The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark
3. The Copenhagen City Heart Study, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, Denmark
4. Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

Correspondence: Professor BG Nordestgaard, Department of Clinical Biochemistry, 54M1, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark. E-mail: brno@heh.regionh.dk

Received 3 April 2009; Accepted 25 June 2009; Published online 4 August 2009.
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Abstract

Cytochrome P450 2C9 (CYP2C9) enzymes metabolize warfarin and arachidonic acid. We hypothesized that the CYP2C9*2 (rs.1799853) and CYP2C9*3 (rs.1057910) polymorphisms with decreased enzyme activity affect risk of subclinical atherosclerosis (reduced ankle brachial index and increased C-reactive protein), ischemic vascular diseases (ischemic heart disease, myocardial infarction, ischemic cerebrovascular disease and ischemic stroke) and death after an ischemic heart disease diagnosis. We genotyped the Copenhagen City Heart Study, a prospective study including 10 398 participants with 30–32 years of follow-up; the Copenhagen General Population Study, a cross-sectional study including 21 629 participants; and the Copenhagen Ischemic Heart Disease Study, a case–control study including 5082 cases and 14 904 controls. CYP2C9 carriers versus noncarriers did not associate with subclinical atherosclerosis. Furthermore, the odds/hazard ratios for ischemic vascular disease did not differ from 1.0 for CYP2C9 carriers versus noncarriers. Finally, we found no altered risk of early death after a diagnosis of ischemic heart disease. For all end points, we could exclude even minor changes in risk of disease with 90% power. In conclusion, in three independent studies totaling more than 52 000 individuals, we found no association between CYP2C9*2 and CYP2C9*3 polymorphisms and risk of subclinical atherosclerosis, ischemic vascular disease or death after ischemic heart disease.