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 (PON1). We studied the association of PON1 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 PON1(192Arg) was higher in cases (0.27) than in controls (0.24, P=0.008), whereas that of PON1(55Leu) was identical (0.26). Compared with PON1(192Gln-Gln), the PON1(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 PON1(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 PON1(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 PON1(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.