Kuremoto Kenichi, Watanabe Yoshiro, Ohmura Hirotoshi, Shimada Kazunori, Mokuno Hiroshi, Daida Hiroyuki
Department of Cardiology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
J Atheroscler Thromb. 2003;10(2):85-92. doi: 10.5551/jat.10.85.
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.
人对氧磷酶（PON1）是一种与高密度脂蛋白（HDL）相关的酶，被认为具有防止脂蛋白氧化的作用。最近，有报道称冠状动脉疾病（CAD）与PON1活性有关。此外，PON1的R/R基因型与CAD风险相关。在本研究中，我们调查了日本受试者的PON1基因型以及脂蛋白氧化易感性，以阐明PON1对动脉粥样硬化的作用。我们研究了179例接受冠状动脉造影的患者，并确定了他们的PON1基因型。在患者至少禁食12小时后采集血液，通过连续超速离心法分离脂蛋白。我们分析了硫代巴比妥酸反应性物质（TBARS），并持续监测了三个基因型组铜诱导的氧化情况。Q/Q、Q/R和R/R的基因型频率分别为21.2%、36.9%和41.9%。PON1多态性明确决定了脂质氧化。PON1的R/R基因型血浆和HDL的TBARS水平显著较低，并且显著延迟了HDL和低密度脂蛋白（LDL）氧化的起始。R/R基因型与CAD的较低患病率相关。PON1基因型明确决定了脂蛋白的氧化修饰，并且可能通过其对日本受试者脂蛋白氧化的保护作用在动脉粥样硬化发病机制中发挥作用。
