Association between cytochrome P450 2C19 polymorphism and clinical outcomes in Chinese patients with coronary artery disease

摘要

Background: Cytochrome P450 (CYP)2C19 is expressed in vascular endothelium and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids, which play a key role in regulating vascular tone. The aim of this study was to investigate whether the genetic functional variant 681G of cytochrome CYP2C19 is associated with adverse cardiovascular outcomes in Chinese patients with coronary artery disease (CAD). Methods: Between July 2008 and September 2009, 654 consecutive patients with CAD were enrolled in this study. All participants underwent CYP2C19 genotyping. The primary study endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Secondary endpoints included the components of the primary endpoint, death from any cause, and recurrent revascularization. Results: The baseline characteristics were well-balanced between carriers (heterozygous *1/ *2, n= 291; homozygous *2/ *2, n= 57) and non-carriers (n= 306) of the CYP2C19*2 variant. During the follow-up period (11.42 ± 4.23 months), the primary endpoint occurred more frequently in homozygous *2/ *2 than in non-carriers (n= 306) of CYP2C19*2 variant (12.28% versus 3.27%; adjusted hazard ratio [HR] = 5.191; 95% confidence interval [CI] = 1.936-13.917; P= 0.001); however, no such increase was evident in heterozygous *1/ *2 patients (4.12% versus 3.27%; adjusted HR = 1.208; 95% CI 0.517-2.822; P= 0.662). Conclusions: The homozygous CYP2C19*2/ *2 genotype is an independent determinant of adverse vascular events in Chinese patients with CAD.