Frequencies of CYP2C19 Polymorphisms in Mexican Mestizo Patients with Coronary or Cerebral Atherosclerosis and Their Association with Residual Platelet Activity on Clopidogrel Treatment.

Background/

Objectives

There is wide variability in the individual response to clopidogrel, which depends on CYP2C19 polymorphisms as well as on intrinsic and extrinsic platelet factors. Clopidogrel resistance has been related to an adverse evolution in patients with coronary artery disease. The aim of this study is to analyze the prevalence of CYP2C19 polymorphisms in Mexican mestizo patients and their relationship with clopidogrel platelet response by means of platelet aggregation.

Methods

Patients who experienced coronary artery disease (CAD) (N = 160) or stroke (N = 11) and received treatment with clopidogrel were analyzed for CYP2C19 alleles *1, *2, *3, and *17. In total, 81 patients were tested for clopidogrel resistance by ADP-induced aggregation in platelet-rich plasma. CYP2C19 polymorphism was expressed as ultrarapid-, normal-, rapid-, normal/intermediate, intermediate, and poor metabolizers, and the clopidogrel response was assessed by platelet aggregation.

Results

The allelic frequencies were 9.6%, 0%, and 11.7% for CYP2C19*2, *3, and *17, respectively. The frequencies of CYP2C19 genotypes were as follows: CYP2C19*1/*1 (62.6%); CYP2C19*1/*17 (19.9%); CYP2C19*1/*2 (12.3%); CYP2C19*2/*17 (2.3%); CYP2C19*2/*2 (2.3%); and CYP2C19*17/*17 (0.6%). Of 81 patients with platelet aggregation, 55.6% were responsive, and 44.4% were resistant to clopidogrel. Clopidogrel resistance had a non-significant trend of association with unfavorable genotypes for metabolism (CYP2C19 *1/*2, *2/*17, and *2/*2) vs. favorable genotypes (CYP2C19 *1/*1, *1/*17, and *17/*17), 64.7% vs. 39.1%, respectively (p = 0.059).

Conclusions

The prevalence of CYP2C19 polymorphisms in Mexican mestizo patients is similar to that of the general population. Clopidogrel resistance is a complex in vitro phenomenon that is not explained by CYP2C19 polymorphisms alone.