Chen Qi, Reis Steven E, Kammerer Candace M, McNamara Dennis M, Holubkov Richard, Sharaf Barry L, Sopko George, Pauly Daniel F, Merz C Noel Bairey, Kamboh M Ilyas
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Am J Hum Genet. 2003 Jan;72(1):13-22. doi: 10.1086/345312. Epub 2002 Nov 26.
Paraoxonase (PON), a high-density lipoprotein-associated enzyme, is believed to protect against low-density lipoprotein oxidation and thus affects the risk of coronary artery disease (CAD). Three polymorphisms in the PON1 (Leu55Met and Gln192Arg) and PON2 (Ser311Cys) genes have been shown to be associated with the risk of CAD in several European or European-derived populations. In the present study, we examined the associations between these three markers and the severity of CAD as determined by the number of diseased coronary artery vessels in 711 subjects (589 whites and 122 blacks) from the Women's Ischemia Syndrome Evaluation (WISE) study. WISE is a National Heart, Lung, and Blood Institute-sponsored multicenter study designed to address issues related to ischemic-heart-disease recognition and diagnosis in women. Subjects were classified as having normal/minimal CAD (<20% stenosis), mild CAD (20%-49% stenosis), and significant CAD (>/=50% stenosis). The women who had >/=50% stenosis were further classified into groups with one-, two-, or three-vessel disease if any of the three coronary arteries had diameter stenosis >/=50%. No significant association was found between the PON polymorphisms and stenosis severity in either white or black women. However, among white women, when data were stratified by the number of diseased vessels, the frequency of the PON1 codon 192 Arg/Arg genotype was significantly higher in the group with three-vessel disease than in the other groups (those with one-vessel and two-vessel disease) combined (17.02% vs. 4.58%; P=.0066). Similarly, the frequency of the PON2 codon 311 Cys/Cys genotype was significantly higher in the group with three-vessel disease than in the other groups combined (15.22% vs. 4.61%; P=.018). The adjusted odds ratios for the development of three-vessel disease were 2.80 (95% confidence interval 1.06-7.37; P=.038) for PON1 codon 192 Arg/Arg and 3.68 (95% confidence interval 1.26-10.68; P=.017) for PON2 codon 311 Cys/Cys. Our data indicate that the severity of CAD, in terms of the number of diseased vessels, may be affected by common genetic variation in the PON gene cluster, on chromosome 7.
对氧磷酶（PON）是一种与高密度脂蛋白相关的酶，被认为可防止低密度脂蛋白氧化，从而影响冠状动脉疾病（CAD）的风险。在几个欧洲或欧洲裔人群中，已证实PON1基因（Leu55Met和Gln192Arg）和PON2基因（Ser311Cys）中的三种多态性与CAD风险相关。在本研究中，我们在来自女性缺血综合征评估（WISE）研究的711名受试者（589名白人及122名黑人）中，研究了这三种标志物与CAD严重程度之间的关联，CAD严重程度由病变冠状动脉血管数量确定。WISE是一项由美国国立心肺血液研究所资助的多中心研究，旨在解决与女性缺血性心脏病识别和诊断相关的问题。受试者被分类为患有正常/轻度CAD（狭窄<20%）、轻度CAD（狭窄20% - 49%）和重度CAD（狭窄≥50%）。狭窄≥50%的女性若三支冠状动脉中任何一支的直径狭窄≥50%，则进一步分为单支血管病变、双支血管病变或三支血管病变组。在白人或黑人女性中，未发现PON多态性与狭窄严重程度之间存在显著关联。然而，在白人女性中，当按病变血管数量分层数据时，三支血管病变组中PON1密码子192 Arg/Arg基因型的频率显著高于其他组（单支血管病变和双支血管病变组）合并后的频率（17.02%对4.58%；P = 0.0066）。同样，三支血管病变组中PON2密码子311 Cys/Cys基因型的频率显著高于其他组合并后的频率（15.22%对4.61%；P = 0.018）。PON1密码子192 Arg/Arg发生三支血管病变的调整优势比为2.80（95%置信区间1.06 - 7.37；P = 0.038），PON2密码子311 Cys/Cys为3.68（95%置信区间1.26 - 10.68；P = 0.017）。我们的数据表明，就病变血管数量而言，CAD的严重程度可能受7号染色体上PON基因簇常见基因变异的影响。
