R/R Genotype of Human Paraoxonase(PON1) is More Protective against Lipoprotein Oxidation and Coronary Artery Disease in Japanese Subjects.

Abstract

Human paraoxonase (PON1) is an high-density lipoprotein (HDL) -associated enzyme that is proposed to protect against the oxidation of lipoproteins. Recently, the association of coronary artery disease (CAD) and PON1 activity was reported. Furthermore, the R/R genotype of PON1 has been related to the risk for CAD. In this study we investigated the PON1 genotype and susceptibility to lipoprotein oxidation to elucidate the contribution of PON1 to atherosclerosis in Japanese subjects. We studied 179 patients who underwent coronary angiography and their PON1 genotypes were determined. Lipoproteins were obtained from a patient's blood after at least 12 hours fasting and were separated with sequential ultracentrifugation. We analyzed the thiobarbituric acid reactive substances (TBARS) and continuously monitored the copper-induced oxidation three genotype groups. Genotype frequencies of Q / Q, Q / R, and R / R were 21.2%, 36.9%, and 41.9%, respectively. PON1 polymorphism clearly determined the lipid oxidation. The R/R genotype of PON1 had significantly lower levels of plasma and HDL TBARS and significantly retarded the initiation of oxidation in HDL and low-density lipoprotein (LDL). The R/R genotype was related to the lower prevalence of CAD. The PON1 genotype clearly determined the oxidative modification of lipoproteins and may play a role in the pathogenesis of atherosclerosis via its protective effect against lipoprotein oxidation in Japanese subjects. J Atheroscler Thromb, 2003; 10: 85-92.

Serum PON-1 Activity but not Q192R Polymorphism is Related to the Extent of Atherosclerosis

“…To date, multiple studies have examined the association between PON1 polymorphism and CAD 4, 13, [15][16][17][18][19][20][21][22][23][24][25][26] ; however, the vast ma- jority of studies neither concurrently assessed PON1 activity nor its relevance with the extent of angiographically documented atherosclerosis. In this study, we aimed at evaluating the relationship of PON1 (Q192R polymorphism and activity) with both CAD risk and the extent and severity of the disease.…”

“…R allozyme is less efficient at preventing the oxidation of LDL than the Q allozyme because of the decreased hydrolysis of lipid peroxides 13,14) . Hypothesized differences in the ability of the polymorphic forms to protect the oxidation of LDL have led to numerous studies attempting to determine the relationship between PON1 polymorphism and cardiovascular disease 4,13,[15][16][17][18][19][20][21][22][23][24][25][26] . These studies have yielded apparently conflicting results.…”

Lower HDL-cholesterol among healthy middle-aged Japanese-Brazilians in São Paulo compared to Natives and Japanese-Brazilians in Japan

“…Levels of HDLcholesterol in the Japanese population are higher than those reported in Caucasian populations [4,5]. This favorable lipid profile may be one of the explanations for the lower morbidity of CHD in Japanese populations [6]. Also, there is a growing consensus in support of high HDL-cholesterol as an additional therapeutic target to promote longevity [7].…”

HDL2 Can Inhibit Further Oxidative Modification of Partially Oxidized LDL

“…The results obtained in the present study have confirmed previous suppositions 16) . It is known that the presence of anti-oxidative vitamins, such as ubiquinol-10, and anti-oxidative enzymes, paraoxisonase [32][33][34] , platelet-activating factoracetylhydrolase 35,36) and glutathione peroxidase 37) in HDL, suppresses the formation of lipid peroxides.…”