Association with PAF-acetylhydrolase gene polymorphism with peripheral arterial occlusive disease

血浆纤溶酶原激活物-乙酰水解酶(PAF-AH)基因外显子9的G^&lt；994&Gt；→T基因多态性及由此导致的酶活性缺陷在日本、土耳其及邻近国家被发现。本研究的目的是评估基因多态性和高胆固醇血症对动脉粥样硬化风险的联合作用。我们进行了一项病例对照研究，包括150例接受外周动脉闭塞症(PAOD)手术的患者和158名年龄和性别匹配的对照组。通过特定的聚合酶链式反应分析基因组DNA中的突变等位基因。测定两组患者血浆PAF-AH活性。对有/无基因多态或高胆固醇血症的PROD患者进行评估，以了解是否伴有冠状动脉疾病或中风。在PROD患者中，该基因多态的发生率明显更高。正常基因型(GG)患者血浆PAP-AH活性与总胆固醇、低密度脂蛋白水平呈正相关，与高密度脂蛋白呈负相关。然而，在具有这种多态的患者中既没有发现这种相关性，也没有发现相反的关系。与正常基因和正常血脂水平相比，同时存在高胆固醇血症和基因多态性的患者患其他动脉粥样硬化性疾病(即缺血性心脏病或脑梗塞)的相对危险度为11.3(95%CI 6.0~40.3)。

Plasma PAF-acetylhydrolase (PAF-AH) gene polymorphisms (G^<994>→T in exon 9) and the resulting deficiency of enzynie activity were identified in Japan, Turkey and the neighbor countries. The objective of this study was to assess the joint effect of the polymorphism and hypercholesterolemia on risk of atherosclerosis.We performed a case-control study including 150 patients who underwent operation for peripheral arterial occlusive disease (PAOD) and 158 controls matched for age and sex. Genomic DNA was analyzed for the mutant allele by a specific polymerase-chain reaction. Plasma PAF-AH activity was measured in both groups. PROD patients were assessed either with/without polymorphism or hypercholesterolemia in regard to accompaning coronary artery disease or stroke. The prevalence of the polymorphism was significantly more frequent in the patients with PROD. The plasma PAP-AH activity was correlated with total cholesterol and LDL level, and inversely related with HDL in normal genotype (GG) patients. However, neither the correlation nor the inverse relation was found in patients with the polymorphism. Patients with both hypercholesterolemia and the polymorphisms revealed a relative risk for other atherosclerotic disease (i.e. ischemic heart disease or brain infarction) of 11.3 (95 % CI 6.0-40.3) compared with normal genotype and normal lipid level.