Cigarette smoking might weaken the prognostic significance of cytochrome P450 2C19*2 polymorphism in acute myocardial infarction patients

J Cell Mol Med. 2016 Jul;20(7):1247-54. doi: 10.1111/jcmm.12797. Epub 2016 Apr 12.

Abstract

Prognostic significance of cytochrome P450 2C19*2 polymorphism in acute myocardial infarction is still not well investigated. The aim of the study was to determine the relationship between the genetic polymorphism and the outcome of the acute myocardial infarction patients, and to further clarify the impact of smoking on such relationship. Six hundred acute myocardial infarction patients were enrolled. All of them provided blood samples and underwent clopidogrel treatment. The genetic polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism analysis, and the platelet function was assessed using conventional aggregometry. Of the included patients, 287 carried GG wild-type genotypes, 225 carried GA genotypes and 88 carried AA genotypes. The platelet aggregation rate was significantly elevated in the AA genotype patients, mainly in the non-smoking patients (P < 0.001) and the former-smoking patients (P < 0.001). During 5-year follow-up period, after adjusted for multiple confounding factors, AA genotypes were associated with the increase in 5-year mortalities in the non-smoking patients [OR: 7.06, 95% confidence interval (CI): 2.16-11.49] and the former-smoking patients (OR: 4.38, 95% CI: 1.05-9.40), but not in the current-smoking patients (OR: 1.12, 95% CI: 0.60-2.31). In conclusion, the study suggested a potential role of P450 2C19*2 polymorphism as a prognostic indicator in acute myocardial infarction patients. We had also obtained some evidence that current smoking might weaken the prognostic significance of the genetic polymorphism in patients.

Keywords: cytochrome P-450 CYP2C19; genetic polymorphism; myocardial infarction; prognosis; smoking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Cytochrome P-450 CYP2C19 / genetics*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / enzymology*
  • Myocardial Infarction / genetics*
  • Platelet Aggregation / drug effects
  • Polymorphism, Genetic*
  • Prognosis
  • Smoking / adverse effects*
  • Survival Analysis

Substances

  • Adenosine Diphosphate
  • Cytochrome P-450 CYP2C19