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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2120.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Sucharita Sen-Banerjee; Xinia Siles; Hannia Campos

From the Department of Nutrition (S.S.-B., H.C.), Harvard School of Public Health, Boston, Mass, and the Salud Coronaria project, Institute of Health Research (X.S., H.C.), University of Costa Rica, San Pedro.

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 (GlnArg) and 55 (MetLeu) 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 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 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 PON1₁₉₂ and smoking status was statistically significant (P=0.04). Thus, the PON1₁₉₂ but not the PON1₅₅ gene polymorphism is associated with an increased risk of MI. This association is not evident among smokers.

Key Words: coronary heart disease • genetic epidemiology • paraoxonase • antioxidants • lipoproteins

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