title: Allelic variants of cytochromes P450 2C modify the risk for acute myocardial infarction.
abstract: Cytochromes P450 (CYP) 2C8 and 2C9 are polymorphic enzymes responsible for the biosynthesis of vasoactive substances from arachidonic acid including endothelium-derived hyperpolarizing factor. Inter-individual differences in the action of these substances might be important in the pathogenesis of cardiovascular diseases such as acute myocardial infarction (AMI) and hypertension. This study describes the relationship between genetic variants of CYP2C8 and CYP2C9, and morbidity in myocardial infarction in a large Swedish patient material. The study included 1172 AMI patients and 1503 control subjects (matched by age, sex and residential area) who participated in the Stockholm Heart Epidemiology Program (SHEEP). Genotyping was performed by allelic discrimination using a 5'-nuclease assay for the CYP2C8 and CYP2C9 variants. To estimate associations to AMI risks, odds ratios (OR) with 95% confidence intervals (CI) were calculated. The frequencies of CYP2C8*1, 2C8*3, 2C9*1, 2C9*2 and 2C9*3 variants in the control group were 0.91, 0.095, 0.83, 0.11 and 0.065, respectively. The risk of AMI in the female individuals carrying the *2 or *3 variant alleles of CYP2C9 and that of all individuals carrying the *3 variant of CYP2C8 was higher [OR (95% CI): 1.3 (1.0-1.9), P = 0.09; 1.5 (1.0-2.2), P = 0.06 and 1.2 (1.0-1.5), P = 0.07, respectively] compared to the groups with CYP2C8*1 and CYP2C9*1. Possession of rare genetic variants of the CYP2C8 and CYP2C9 genes in females is associated with a modest increase in risk of AMI. This might be related to genetic differences in the formation of endogenous vasoregulating eicosanoids.
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden.
authors.forename: Umit
authors.initials: U
authors.lastname: Yasar
authors.forename: Anna M
authors.initials: AM
authors.lastname: Bennet
authors.forename: Erik
authors.initials: E
authors.lastname: Eliasson
authors.forename: Stefan
authors.initials: S
authors.lastname: Lundgren
authors.forename: Björn
authors.initials: B
authors.lastname: Wiman
authors.forename: Ulf
authors.initials: U
authors.lastname: De Faire
authors.forename: Anders
authors.initials: A
authors.lastname: Rane
mesh_terms: D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology* / Q000235:genetics; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
chemical_list: D017931:DNA Primers; D003577:Cytochrome P-450 Enzyme System