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 (chi2=2.0; P<0.3). Distribution of PON1 genotypes in CAD+ were not significantly different from those in CAD- (chi2=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.
Subject(s)
Arginine/genetics , Coronary Disease/enzymology , Esterases/genetics , Glutamine/genetics , Polymorphism, Genetic , Adult , Aryldialkylphosphatase , Coronary Disease/genetics , Female , Gene Frequency , Genotype , Humans , Italy , Lipids/blood , Male , Middle AgedABSTRACT
BACKGROUND: The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene has been proposed as a genetic marker of the risk of ischaemic heart disease. However, the relationships between ACE genotypes, the development of coronary atherosclerosis and the occurrence of major coronary events are still controversial. METHODS: To investigate whether the ACE I/D (insertion/deletion) polymorphism predicts the risk of coronary stenosis and myocardial infarction (MI), ACE genotypes were determined in 394 consecutive patients who underwent coronary angiography. The presence determined in 394 consecutive patients who underwent coronary angiography. The presence of coronary artery disease (CAD) (defined by > 50% stenosis) was detected in 236 patients (CAD+); 85 of these individuals had a history of MI. Patients with coronary stenosis < 10% (n = 158) served as controls (CAD-). ACE genotypes were determined by agarose gel sizing after polymerase chain reaction (PCR) amplification. RESULTS: The distribution of ACE genotypes in CAD+ patients was not significantly different from that in CAD-patients (chi 2 = 2.63, P < 0.27). After controlling for other coronary risk factors, no significant increase in risk of CAD or MI was found to be associated with the D allele, regardless of whether the D allele was assumed to have a dominant, a codominant or a recessive effect. Similar results were observed in CAD+ patients at lower risk because of low body mass index and apolipoprotein B concentrations. Smoking, apolipoprotein B and history of hypertension were found to be independent predictors of CAD and MI. CONCLUSION: Our study did not provide evidence of a significant association between ACE genotypes and the development of coronary atherosclerosis. It also failed to support a role of ACE I/D polymorphism in favouring the conversion of coronary stenosis to MI.
