Key result
CYP2C19*2 AA genotype linked to ~7.1-fold higher 5-year mortality in non-smokers after AMI.
Why the study?
Does the cytochrome P450 2C19*2 polymorphism affect 5-year mortality in acute myocardial infarction patients treated with clopidogrel, and how does smoking impact this relationship?
Cohort (n=900)
No
Does the cytochrome P450 2C19*2 polymorphism affect 5-year mortality in acute myocardial infarction patients treated with clopidogrel, and how does smoking impact this relationship?
Odds Ratio: 7.06 (95% CI 2.16–11.49)
The P450 2C19*2 AA genotype is a strong prognostic indicator for 5-year mortality in AMI patients on clopidogrel, but this effect appears to be weakened by current smoking.
CYP2C19*2 AA genotype associated with higher mortality only in non- and former-smoking AMI patients on clopidogrel; leaves open clinical utility of genotyping.
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.
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Zhang et al. (2016) conducted a cohort in Acute myocardial infarction (n=900). CYP2C19*2 polymorphism (AA genotype) vs. CYP2C19 wild-type (GG genotype) was evaluated on 5-year mortality (death as a result of recurrent myocardial infarction) (OR 7.06, 95% CI 2.16-11.49). The CYP2C19*2 AA genotype increased 5-year mortality in non-smoking (OR 7.06) and former-smoking (OR 4.38) AMI patients on clopidogrel, but this prognostic effect was absent in current smokers.
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