© 1998 American Heart Association, Inc.
Original Contributions |
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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