基因学干预研究:血红素氧合酶1微卫星多态性表达水平上调的作用(英文)

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背景:人类血红素氧合酶1(HemeOxygenase-1,HO-1)基因启动子区域有一双核苷酸(GT)n重复序列,有高度多态性,又称为微卫星多态性,体外实验表明通过测定GT重复次数可间接了解人体内HO-1的表达水平。目的:探讨HO-1基因启动子双核苷酸GTn重复序列的微卫星多态性与冠状动脉支架术后再狭窄的关系。设计:以接受冠状动脉支架置入术的冠心病患者为研究对象的病例对照研究。单位:一所大学医院的心内科病房。对象:研究对象为1996-04/2002-05北京大学第一医院心内科病房成功接受冠状动脉支架置入术的冠心病患者,共118例。纳入标准:支架术后3个月以上行冠状动脉造影随访的冠心病患者;排除标准:冠状动脉造影显示原靶病变管腔直径狭窄<50%和冠状动脉造影随访时间<3个月的冠心病患者。入选患者年龄(62±10)岁,男92例,女26例,所有患者均签署知情同意书。根据美国心肺血液协会的标准定义,将患者分为支架内再狭窄组与无再狭窄组,分别为68例和50例。方法:提取患者外周血DNA,经PCR扩增HO-1微卫星序列后采用Spreadex凝胶电泳来进行基因分型。主要观察指标:HO-1基因启动子微卫星基因型频率及其与再狭窄的关系。结果:携带GT重复<25次等位基因患者的再狭窄率为47.5%,携带两条GT重复均≥25次等位基因患者的再狭窄率为68.4%(P<0.05)。 BACKGROUND: The human hemeoxygenase-1 (HO-1) gene promoter region has a single nucleotide (GT) n repeat sequence with a high degree of polymorphism, also known as microsatellite polymorphism. In vitro experiments It indicates that the level of HO-1 expression in human body can be indirectly understood by measuring the number of GT repetitions. Objective: To investigate the relationship between the microsatellite polymorphism of the dinucleotide dinucleotide repeats (GTn) of HO-1 gene promoter and the restenosis after coronary stenting. DESIGN: A case-control study of coronary heart disease patients undergoing coronary stenting. Unit: a university hospital cardiology ward. PARTICIPANTS: A total of 118 patients with coronary heart disease undergoing coronary stenting were enrolled in the Department of Cardiology, First Hospital of Peking University from April 1996 to May 2002. Inclusion criteria: patients with coronary heart disease who underwent coronary angiography at least 3 months after stent implantation; Exclusion criteria: Coronary angiography showed coronary stenosis of less than 50% of the original target lesion lumen diameter and coronary artery angiography follow-up time <3 months patient. Patients aged 62 ± 10 years, including 92 males and 26 females, all received informed consent. According to the American Heart Lung Blood Association standard definition, patients were divided into two groups: restenosis group and no restenosis group, 68 and 50 respectively. Methods: DNA from patients’ peripheral blood was extracted. The microsatellite sequence of HO-1 was amplified by PCR and genotyped by Spreadex gel electrophoresis. MAIN OUTCOME MEASURES: The frequency of microsatellite genotype of HO-1 gene promoter and its relationship with restenosis. Results: The restenosis rate was 47.5% in patients with GT repeat <25 alleles, and 68.4% (P <0.05) in patients with two GTs with ≥25 repetitions.
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