The risk of myocardial infarction in patients with reduced activity of cytochrome P450 2C9.
OBJECTIVE
The aim of the present follow-up study was to investigate whether the enzyme activity of the human cytochrome P450 (CYP) 2C9 isoenzyme is associated with myocardial infarction.


METHODS
We investigated whether the variant alleles CYP2C9*2 and CYP2C9*3 or the use of CYP2C9 substrates or inhibitors was associated with an increased risk of myocardial infarction in 2210 men and 3534 women from the Rotterdam Study, a prospective population-based cohort study of individuals aged 55 years or older.


RESULTS
In women, the use of CYP2C9 substrates or inhibitors was significantly associated with incident myocardial infarction with a hazard ratio of 2.48 (95% confidence interval: 1.55-3.96). Within the group of female carriers of a variant allele, the use of CYP2C9 substrates or inhibitors was associated with a fourfold increased risk of myocardial infarction (hazard ratio 3.86, 95% confidence interval: 1.93-7.75), as compared with non-use. Neither the use of CYP2C9 inhibitors or substrates nor the variant CYP2C9 alleles were associated with an increased risk of myocardial infarction in men.


CONCLUSIONS
Drugs that are metabolized by CYP2C9 increase the risk of myocardial infarction in women. This risk was even higher in women with allelic variants of CYP2C9 with reduced enzyme activity.
Visser
Loes E
LE
Department of Epidemiology, Erasmus MC, Rotterdam, Inspectorate for Health Care, The Hague, The Netherlands.
van Schaik
Ron H N
RH
Jan Danser
Alexander H
AH
Hofman
Albert
A
Witteman
Jacqueline C M
JC
van Duijn
Cornelia M
CM
Uitterlinden
André G
AG
Pols
Huibert A P
HA
Stricker
Bruno H Ch
BH
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D014644:Genetic Variation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000201:enzymology* / Q000209:etiology / Q000235:genetics*; D009426:Netherlands; D010597:Pharmacogenetics; D011446:Prospective Studies; D012307:Risk Factors; D012727:Sex Characteristics
C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases