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内皮素-1 Lys198AsnT等位基因与冠心病关系的研究

The Study on the Association of T Allele Gene of ET-1 Lys198Asn and Coronary Heart Disease

【作者】 杨燕

【导师】 王敬萍;

【作者基本信息】 山西医科大学 , 心血管内科学, 2011, 硕士

【摘要】 目的:研究探讨内皮素-1(endothelin-1,ET-1)Lys198Asn T等位基因与冠心病(coronary heartdisease,CHD)的关系,及其对血清内皮素-1水平的影响。探讨汉族人群冠心病的易感基因;开发快速、特异的人群基因型检测方法,检查高危人群基因型,用于采取相应措施降低冠心病发病风险。方法:用酶联免疫吸附测定法检测冠心病组和对照组血清ET-1水平。用聚合酶链反应-引物特异性片断长度多态性(PCR-SSP)方法检测Lys198Asn基因型。标本入选条件:冠心病组160例,包括不稳定型心绞痛、急性ST段抬高心肌梗死和非ST段抬高心肌梗死患者,均行冠脉造影检查,至少一支冠状动脉狭窄≥70%,所有病例均符合WHO诊断标准。对照组80例,选自健康体检人群,通过病史、体检、心电图和胸片排除器质性心脏病。结果:1. ET-1基因G198T基因型比较:冠心病组GT+TT基因型频率(19.375%)显著高于对照组(5.00%),差异有统计学意义(χ2 =8.847,P <0.05),基因型频率的相对风险分析,GT+TT基因型患冠心病的风险是GG基因型的4.566倍(OR=4.566, 95%CI: 1.68,12.40)。2.冠心病组G、T等位基因频率与对照组比较:T等位基因频率显著高于对照组,差异有统计学意义(χ2 =9.659,P<0.05,OR=4.6364,95%CI: 1.953~8.052)。3.血清ET-1水平比较:冠心病组血清ET-1水平[(27.8±7.3)ng/L]高于对照组[(12.5±8.1)ng/L],差异有统计学意义(P<0.01);冠心病组GT+TT基因型携带者的血清ET-1水平[(33.3±7.9)ng/L]显著高于同组GG基因型者[(24.2±7.5)ng/ L],(P<0.05)差异有统计学意义。结论:1. ET-1基因G198T基因型多态性会影响ET-1的表达。2. G198T基因多态性使得冠心病的发病危险性增加, T等位基因可能是冠心病的易感性标志;3. G198T基因型或可为筛选冠心病高危人群提供有价值的参考依据。T等位基因可否作为冠心病发生的遗传性标志,尚需更多的大样本病例研究加以证实。

【Abstract】 Objective To investigate the association between the Polymorphism of ET-1 Lys198Asngene and coronary heart disease(CHD) in Hans of Chinese . Genotype is used to check high-riskgroups in order to take appropriate measures to reduce the risk of coronary heart disease.Methods 160 patients with CHD and 80 volunteers without documented evidence of CHDwere subjected to a case-control study.ET-1 G198T polymorphism in the CHD group and controlgroup respectively was detected by using the method of polymerase chain reaction-restrictionfragment length polymorphisms. To detect the expression of ET-1 by the means ofenzyme-linked immunosorbent assay(ELISA)Results (1)For the endothelin-1 G198T gene polymorphism, the frequencies of GT+TTgenotype were 19.375% in the CHD group,significantly higher than those in the control group(5.0%,P<0.05). The frequency of T allele genotype is significantly higher than in controls. Thedifferency is significant (χ2 =9.659,P<0.01). The levels of ET-1 selectin in the CHD group[ (27.8±7.3 ) ng/ L ] were significantly higher than those in the cont rol group [ (19.5±8.1) ng/L ,P < 0.01 ] .Conclusion The Polymorphism of ET-1 Lys198Asn gene could be related to CHD inchianese han. T allele might be a marker for susceptibility of CHD.

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