Association between CYP2C19*2/*3 Polymorphisms and Coronary Heart Disease

Curr Med Sci. 2019 Feb;39(1):44-51. doi: 10.1007/s11596-019-1998-2. Epub 2019 Mar 13.

Abstract

This study sought to explore the relationship between cytochrome P450 2C19 (CYP2C19) *2/*3 polymorphisms and the development of coronary heart disease (CHD), and to evaluate the influence of the single nucleotide polymorphisms (SNPs) on the occurrence of adverse clinical events in CHD patients. A total of 231 consecutive patients candidate for percutaneous coronary intervention genotyped for CYP2C19*2 (681G>A) and *3 (636G>A) polymorphisms were enrolled. The adverse clinical events were recorded during a follow-up period of 14 months. The incidence of CHD, according to coronary angiography, was significantly higher (P=0.025) in CYP2C19*2 carriers group. Stepwise binary logistic regression analysis revealed that among factors that potentially influenced the presence of CHD (age>60 years, gender, BMI, etc.), CYP2C19*2 carriers (OR 1.94, 95% CI: 1.08-3.50, P=0.028) and male gender (OR 2.74, 95% CI: 1.58-4.76, P=0.001) were independent predictors, which were associated with the presence of CHD. The follow-up results showed that the incidence of adverse cardiovascular events within 14 months of discharge was significantly higher in the CYP2C19*2 carriers than in the non-carriers (21.6% vs. 6.3%, P=0.019). The results of the multivariate Cox proportional hazards model showed that CYP2C19*2 loss-of-function was the only independent factor which predicted the coronary events during the follow-up period of 14 months (OR=3.65, 95% CI 1.09-12.25, P=0.036). The adverse impact of CYP2C19*2 polymorphisms was found not only in the risk of the presence of CHD, but also in the adverse cardiovascular events in CHD patients during the follow-up period of 14 months. However the same influence was not found in CYP2C19*3 mutation in Chinese Han population.

Keywords: clopidogrel; coronary heart disease; cytochrome P450 2C19; polymorphisms.

MeSH terms

  • Age Factors
  • Aged
  • Coronary Disease / genetics*
  • Coronary Disease / surgery*
  • Cytochrome P-450 CYP2C19 / genetics*
  • Female
  • Genetic Association Studies / methods*
  • Genetic Predisposition to Disease
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention / adverse effects
  • Polymorphism, Single Nucleotide
  • Sex Factors

Substances

  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19