Tobacco smoking modifies association between Gln-Arg 192 polymorphism of human paraoxonase gene and risk of myorcardial infarction

Abstract

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 (PON!). 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 PON/192A, was higher in cases (0.27) than in controls (0.24, P=0.008), whereas that of PON/55L,„ was identical (0.26). Compared with PON/192Gh.fr0i6, the PON1 mks 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 PON155 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 PON/ inug 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 PON1192 and smoking status was statistically significant (P=0.04). Thus, the PONlm but not the PON/55 gene polymorphism is associated with an increased risk of MI. This association is not evident among smokers