The Gln-Arg192 Polymorphism of Human Paraoxonase Gene Is Not Associated With Coronary Artery Disease in Italian Patients

From the Istituto di Terapia Medica Sistematica (D.O., A.M., F.C., R.C., G.R., M.A.), II Cattedra di Cardiologia (G.P., A.C., P.P.C.) and Istituto di Chirurgia del Cuore e dei Grossi Vasi (G.P.), Università di Roma "La Sapienza," and the Laboratorio di Epidemiologia e Biostatistica, Istituto Superiore di Sanità (F.S.), Rome, Italy.

Correspondence to Marcello Arca, MD, Istituto di Terapia Medica Sistematica, Università di Roma "La Sapienza," Policlinico Umberto I, Viale del Policlinico, 00161 Rome, Italy. E-mail itmsricci{at}caspur.it

Abstract—Serum paraoxonase (PON) is an HDL-bound enzyme protecting LDL from oxidation. A common polymorphism of the paraoxonase gene (PON1) involving a Gln-to-Arg interchange at position 192 has been demonstrated to modulate PON activity toward paraoxon, a nonphysiological substrate; Arg192 (allele B) is associated with higher activity than Gln192 (allele A). This polymorphism has been proposed as a genetic marker of risk for coronary artery disease (CAD). However, the relationships between codon 192 PON1 genotypes, coronary atherosclerosis, and the occurrence of myocardial infarction (MI) are still controversial. PON1 genotypes were determined in 472 consecutive subjects (>40 years old) who underwent coronary angiography. CAD (>50% stenosis) was detected in 310 subjects (CAD+); 162 subjects with <10% stenosis served as controls (CAD-). We also evaluated 204 randomly selected individuals as population controls. PON1 genotypes were determined by PCR and AlwI restriction enzyme digestion. Frequencies of alleles A and B were 0.70 and 0.30 in angiographically assessed subjects and 0.73 and 0.27 in population controls, respectively (²=2.0; P<0.3). Distribution of PON1 genotypes in CAD+ were not significantly different from those in CAD- (²=2.10; P<0.3). Similarly, no differences were observed in the subgroup of CAD+ with MI nor in that at higher oxidative risk (smokers and/or diabetics). After controlling for other coronary risk factors, no association was found between PON1 alleles and the presence of CAD. PON1 AA genotype was associated with reduced concentration of apolipoprotein B–containing triglyceride-rich lipoproteins. This study did not provide evidence of a significant association between codon 192 PON1 genotypes and coronary atherosclerosis in Italian patients. However, it did confirm that the PON1 low-activity allele is associated with a less atherogenic lipid profile.

Key Words: coronary artery disease • genetics • paraoxonase • myocardial infarction • LDL oxidation

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