OX40L/OX40基因组变异与早发冠心病风险之间的关系  

Relationship Between Variation of OX40L/OX40 Gene Group and the Risk of Premature Coronary Artery Disease

作　　者：赵文强[1] 王俊[2] 孙光明[2] 欧阳星文[1] 谢红珍[2] 陈辉[2] 吴艳君[2] 

机构地区：[1]安徽省立友谊医院心内科,安徽省合肥市230041 [2]江苏大学第四附属医院心内科

出　　处：《中国循环杂志》2010年第6期432-436,共5页Chinese Circulation Journal

基　　金：镇江市科技局社会发展基金资助项目(SH2006048)

摘　　要：目的:研究OX40L/OX40基因组变异与早发冠心病风险之间的关系。方法:用序列特异性引物—聚合酶链反应技术对243例年龄<55岁早发急性冠状动脉(冠脉)综合征(PACS)的患者为PACS组、209例早发稳定性心绞痛(PSAP)为PSAP组和138例对照组检测OX40L基因rs3850641 A/G变异位点和OX40基因rs2298212 G/A位点变异的基因型、等位基因及其单倍型;用冠脉造影测量病变血管支数和狭窄程度积分;用酶链免疫吸附法(ELISA)测试血浆可溶性OX40L(sOX40L)、血管细胞黏附分子1(VCAM-1);用散射比浊法测试血浆C反应蛋白(CRP)水平;分析OX40L/OX40基因变异与冠心病风险、冠脉病变程度和血浆3个细胞因子之间的关系。结果:OX40L GG基因型和G等位基因发生PACS风险比AA基因型和A等位基因显著增高(OR=1.99,1.83;P=0.021,P=0.0001);而OX40 A等位基因比G等位基因发生PACS风险显著降低(OR=0.49,P=0.002);单倍型GGGG比AAGG(野生型)的PACS风险显著增加(OR=2.11,P=0.033);在4种高危因素(高血压、高脂血症、糖尿病和吸烟)被校正后OX40L G等位基因和GG基因型及单倍型GGGG与PACS风险仍具有独立关联性(OR=1.97、1.78、2.01,P=0.026、0.001、0.038),OX40 A等位基因和AA基因型对PACS风险仍有独立的关联性(OR=0.31、0.45;P=0.043、0.0001);OX40L基因型GG+AG比AA型血管病变支数≥3支的百分率和狭窄程度积分均显著增加;OX40基因型AA+GA比GG型血管病变支数≥3支的百分率和狭窄程度积分显著减低;差异均有统计学意义(P<0.05)。基因型变异与炎性细胞因子表达:OX40L基因型GG+AG比AA型血浆可溶性OX40L、C反应蛋白、血管细胞黏附分子1水平均显著增高;OX40基因型AA+GA比GG型三指标显著降低。差异均有统计学意义(P<0.05)。结论:OX40L/OX40基因组变异可能与PACS风险、冠脉病变程度及炎性因子的表达的正反调节有关。Objective：To investigate the relationship between genetic variations of OX40L/OX40 and the risk of premature coronary artery disease（PCAD）.Methods：Our research included three groups,PACS group,243 patients with premature acute coronary syndrome（PACS） younger than 55 years of age,PSAP group,209 patients with premature stable angina pectoris（PSAP） and Control group of 138 subjects.Sequence specific primers-polymerase chain reaction（PCR-SSP） was performed to detect genotypes,alleles and halo types of A/G variant in OX40L rs3850641 SNP loci and G/A variant in OX40 rs2298212 SNP loci.Diseased vessel number（DVN） and stenostic severity integral（SSI） were examined by coronary angiography,and serum levels of soluble OX40L（sOX40L）,C-reactive protein（CRP）,vascular cell adhesion molecule-1（VCAM-1） were tested by ELISA and nephelometry.The relationship between OX40L/OX40 gene variants and PCAD risk,DVN,SSI and plasma levels of three cytokines were analyzed.Results：OX40L gene A/G variant and OX40 gene G/A variant were significantly associated with PACS risk but in-significantly related with PSAP risk.GG genotypes and G allele in OX40L showed the higher risk of PACS than their wild types（OR=1.99,1.83;P=0.021,P=0.0001） but AA genotypes and A allele in OX40 had the lower risk of PACS than their wild types.Risk of PACS in Halo type GGGG was higher than that in wild type（OR=2.11,P=0.033）.A/G variant in OX40L and G/A variant in OX40 presented the independent role for PACS risk after four risk factors of high blood pressure,high blood lipids,diabetes and smoking were corrected by statistic analysis.Variant genotypes in OX40L had significantly higher DVN,SSI,sOX40L,CRP and VCAM-1 than the wild types while variant genotypes in OX40 showed inverse changes of those five index in OX40L.Those differences had the statistic meawing.Conclusion： Genetic variations of OX40L/OX40 might be related with PACS risk,coronary lesion severity and expression of inflammatory cytokines.

关 键 词：冠状动脉疾病 聚合酶链反应 基因型 OX40配体 

分 类 号：R541[医药卫生—心血管疾病]