Tobacco Smoking Modifies Association Between Gln-Arg192 Polymorphism of Human Paraoxonase Gene and Risk of Myocardial Infarction

Paraoxonase, a high density lipoprotein-associated human serum enzyme, plays a role in atherosclerosis by protecting against lipid peroxidation. Its activity is modulated by 2 common amino acid polymorphisms at positions 192 (Gln-->Arg) and 55 (Met-->Leu) in the paraoxonase gene (P:ON1). We studied the association of P:ON1 polymorphisms and myocardial infarction (MI) in a population-based study consisting of 492 cases and 518 controls matched for age, sex, and area of residence, all living in Costa Rica. The allele frequency of P:ON1(192Arg) was higher in cases (0.27) than in controls (0.24, P:=0.008), whereas that of P:ON1(55Leu) was identical (0.26). Compared with P:ON1(192Gln-Gln), the P:ON1(192Arg) allele was associated with an increased risk of MI (odds ratio [OR] 1.36, CI 1.06 to 1.75), and this association was independent of the P:ON1(55) polymorphism, which was not associated with MI (OR 1.10, CI 0.82 to 1.48). Adjustment for lipid and nonlipid risk factors strengthened the association between P:ON1(192Arg) and the risk of MI (OR 1.51, CI 1.13 to 2.03). Interestingly, this association was evident only among nonsmokers (OR 1.90, CI 1.29 to 2.79): there was no evidence of an association in smokers (OR 0.95, CI 0.57 to 1.79). The interaction between P:ON1(192) and smoking status was statistically significant (P:=0.04). Thus, the PON1(192) but not the PON1(55) gene polymorphism is associated with an increased risk of MI. This association is not evident among smokers.