Genotypes of Common Polymorphisms in the PON1 Gene Associated with Paraoxonase Activity as Cardiovascular Risk Factor

Abstract

Paraoxonase-1(PON1) exhibits hydrolytic activity and prevents the oxidation of high and low-density lipoproteins. Polymorphisms in the PON1 gene have been associated with variations in paraoxonase activity and with the risk of coronary artery disease (CAD). This study analyzed the association between the frequencies of genotypes of the L55M and Q192R SNPs in the PON1 gene with the PON1 activity and with CAD risk factors. Women, determined by body composition, biochemical markers, and arylesterase (AREase) and paraoxonase (CMPase) activities were studied. Genotyping of L55M and Q192R polymorphisms was performed by TaqMan. Seventeen studies were used in the meta-analysis. A significant decrease in PON1 activity in carrying the LM/MM and QQ genotypes is identified, correlations are found between the AREase activity with glucose, cholesterol and atherogenic risk index. Carriers of the LM or MM genotype were related with obesity (OR=1.6; p=0.039), and the MQ haplotype has an effect on the decrease in AREase (β=‒22.4; p<0.001) and CMPase (β=‒3.8; p<0.001). In addition, a lower proportion of Native American admixture was observed in women with LM or MM genotype, while it was higher for the European proportion compared with the LL genotype (p<0.001). The LL-L55M and QR-Q192R genotypes are identified as the most frequently in the different states or cities of the country, and genotypic proportions are different, probably depending on the genetic structure of the populations. The association that is reported more frequently in the different studies is with enzymatic activity.