Watzinger N, Schmidt H, Schumacher M, Schmidt R, Eber B, Fruhwald F M, Zweiker R, Kostner G M, Klein W
Department of Medicine, Karl Franzens University, Graz, Austria.
Cardiology. 2002;98(3):116-22. doi: 10.1159/000066321.
Published data on the association between paraoxonase1 (PON1) polymorphisms and coronary heart disease (CHD) have yielded controversial results. The objective of this study was to determine the possible relationship between the two human PON1 amino acid variants, the Leu55Met and the Gln192Arg polymorphism, and the risk of CHD in a community-dwelling cohort of European ancestry. PON1 genotypes of 152 women and 151 men out of 1,998 randomly selected individuals aged 44-75 years were determined by polymerase chain reaction-based restriction enzyme digestion. Study participants underwent cardiological examination including a structured clinical interview, resting ECG, exercise testing and echocardiography. The diagnosis of CHD was based on history and/or appropriate findings during cardiac examination. Evidence for CHD was found in 43 (14.2%) study participants. The Leu/Leu (LL), Leu/Met (LM) and Met/Met (MM) genotypes at position 55 were noted in 131 (43.2%), 128 (42.2%) and 44 (14.5%) subjects; the Gln/Gln (QQ), Gln/Arg (QR) and Arg/Arg (RR) genotypes at codon 192 occurred in 167 (55.1%), 118 (38.9%) and 18 (5.9%) individuals, respectively. Homozygosity for the 55L-allele was significantly associated with CHD (p = 0.02), while the Gln192Arg polymorphism had no effect (p = 0.16). Logistic regression analysis demonstrated age (odds ratio 1.06/year), smoking (odds ratio 2.86), HDL cholesterol (odds ratio 0.94/mg/dl) and the paraoxonase LL genotype (odds ratio 2.25) to be significant predictors of CHD. These data suggest that the paraoxonase LL genotype at position 55 may present a risk factor for CHD.
已发表的关于对氧磷酶1（PON1）基因多态性与冠心病（CHD）之间关联的数据产生了有争议的结果。本研究的目的是确定两种人类PON1氨基酸变体Leu55Met和Gln192Arg多态性与欧洲血统社区居住队列中冠心病风险之间的可能关系。通过基于聚合酶链反应的限制性酶切消化法，对1998名年龄在44 - 75岁的随机选择个体中的152名女性和151名男性的PON1基因型进行了测定。研究参与者接受了心脏病学检查，包括结构化临床访谈、静息心电图、运动试验和超声心动图检查。冠心病的诊断基于病史和/或心脏检查期间的适当发现。在43名（14.2%）研究参与者中发现了冠心病的证据。在第55位的Leu/Leu（LL）、Leu/Met（LM）和Met/Met（MM）基因型分别在131名（43.2%）、128名（42.2%）和44名（14.5%）受试者中被检测到；密码子192处的Gln/Gln（QQ）、Gln/Arg（QR）和Arg/Arg（RR）基因型分别出现在167名（55.1%）、118名（38.9%）和18名（5.9%）个体中。第55位L等位基因的纯合性与冠心病显著相关（p = 0.02），而Gln192Arg多态性则无影响（p = 0.16）。逻辑回归分析表明年龄（比值比1.06/年）、吸烟（比值比2.86）、高密度脂蛋白胆固醇（比值比0.94/毫克/分升）和对氧磷酶LL基因型（比值比2.25）是冠心病的显著预测因素。这些数据表明第55位的对氧磷酶LL基因型可能是冠心病的一个危险因素。
