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.
|Keywords||Cohort studies, Cytochrome P450 enzyme system, Myocardial infarction, Single nucleotide polymorphism|
|Persistent URL||dx.doi.org/10.1097/01.fpc.0000236335.57046.c8, hdl.handle.net/1765/37112|
|Journal||Pharmacogenetics and Genomics|
Visser, L.E, van Schaik, R.H.N, Danser, A.H.J, Hofman, A, Witteman, J.C.M, Tikka-Kleemola, P, … Stricker, B.H.Ch. (2007). The risk of myocardial infarction in patients with reduced activity of cytochrome P450 2C9. Pharmacogenetics and Genomics, 17(7), 473–479. doi:10.1097/01.fpc.0000236335.57046.c8