A study Paraoxonase (PON-1) activity and PON-1 Gene Polymorphism in Coronary Artery Disease (CAD)

Abstract

Paraoxonase-1 (PON-1) is an HDL associated enzyme, implicated in the pathogenesis of atherosclerosis by preventing lipid peroxide generation. The population variability in this enzyme activity is attributed to polymorphism in PON-1 gene. Recent reports have suggested that PON-1 Q192R polymorphism is associated with coronary artery disease (CAD) in different ethnic populations. However to this date, there is no published data of such study in Malaysia. The present study looks at PON-1 Q192R gene polymorphism and PON-1 activities among CAD patients in Tengku Ampuan Afzan Hospital, Kuantan. This study consisted of 187 CAD patients and 188 controls. Fasting serum samples were analyzed for PON-1 activities towards paraoxon and phenylacetate as well as for lipid profiles. PON-1 Q192R gene polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum PON-1 activities were found to be lower in CAD patients than in the healthy controls but the results were not significant (p > 0.05). The Q192R polymorphism was significantly associated with CAD where the 192R allele was found to be more frequent in CAD patients than controls (0.618 vs 0.513) with QR genotype being the commonest (45.5%), followed by RR (39.0%) and QQ (15.5%) genotypes. The PON-1 activities were found to be significantly lower in QQ homozygotes followed by QR heterozygotes and RR homozygotes (QQ<QR<RR) in patients and controls (p < 0.05). The PON-1 activities in different PON-1 genotypes were however similar between CAD and healthy controls (p > 0.05). The HDL-C was significantly (p = 0.011) lower [1.13 (1.02, 1.24) vs 1.36 (1.20, 1.52)] while the TG was significantly (p = 0.048) higher [1.88 (1.58, 2.18) vs 1.38 (0.94, 1.82)] in CAD patients as compared to controls. However, only HDL-C was positively and strongly correlated with the PON-1 activities in CAD patients (p < 0.001) but not in controls. In conclusion, the PON-1 Q192R polymorphism is significantly associated with CAD but not the PON-1 activities. A multicentre study may be required to confirm our findings in Malaysian population.