Common polymorphisms in CYP2C9, subclinical atherosclerosis and risk of ischemic vascular disease in 52,000 individuals.
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.
Kaur-Knudsen
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D
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, DK-2730 Herlev, Denmark.
Bojesen
S E
SE
Nordestgaard
B G
BG
D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D065729:Cytochrome P-450 CYP2C9; D003718:Denmark / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007511:Ischemia / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases