Association between the severity of angiographic coronary artery disease and paraoxonase-1 promoter gene polymorphism T[-107] C in Iranian population

ABSTRACT

The oxidation of low-density lipoproteins and cell membrane lipids is believed to play an integral role in the development of fatty streak lesions, an initial step in coronary artery disease [CAD]. Paraoxonase-1 [PON1] is an enzyme associated with the high-density lipoprotein [HDL] particle. PON1 protects LDL from oxidative modification by hydrolyzing lipid peroxides, suggestive of a role for PON1 in the development of CAD. The present study tested the hypothesis that Paraoxonase-1 promoter polymorphism T[-107]C could be a risk factor for severity of CAD in Iranian population. Paraoxonase-1 promoter genotypes were determined in 300 consecutive subjects [> 40 years old] who underwent coronary angiography [150 subjects with >50% stenosis served as cases [CAD+] and 150 subjects with < 20% stenosis served as controls [CAD-]]. PON1 promoter genotypes were determined by PCR and BSTU1 restriction enzyme digestion. CAD+ Subjects did not show any significant differences in the distribution of PON1 promoter genotypes as compared to CAD- Subjects [P = 0.075]. However the analysis of PON1 promoter genotypes distribution showed a higher percentage of [-107] TT among CAD+ compared with CAD- [P = 0.027]. After controlling for other risk factors, the T[- 107]C polymorphism had interaction with age [P = 0.012], but did not show any interaction with other risk factors such as BMI, gender, smoking, diabetes, level of HDL-C, LDL-C, triglyceride and Total cholesterol. These data suggest that the TT genotype may represent a genetic risk factor for Coronary artery disease in Iranian population