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

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>A (*2) 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.