CAJ | 학술논문

背景:人类血红素氧合酶1(Heme Oxygenase-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GT n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).经多元回归分析校正冠心病危险因素及介入治疗的相关影响因素后,两组患者的再狭窄率差异仍有显著性意义(OR=0.418,95%可信区间0.197～0.887,P＜0.05).结论:HO-1基因启动子微卫星多态性与再狭窄相关,对冠心病患者冠状动脉支架置入术后的二级预防有十分重要的意义.
배경:인류혈홍소양합매1(Heme Oxygenase-1,HO-1)기인계동자구역유일쌍핵감산(GT)n중복서렬,유고도다태성,우칭위미위성다태성,체외실험표명통과측정GT중복차수가간접료해인체내HO-1적표체수평.목적:탐토HO-1기인계동자쌍핵감산GT n중복서렬적미위성다태성여관상동맥지가술후재협착적관계.설계:이접수관상동맥지가치입술적관심병환자위연구대상적병례대조연구.단위:일소대학의원적심내과병방.대상:연구대상위1996-04/2002-05북경대학제일의원심내과병방성공접수관상동맥지가치입술적관심병환자,공118례.납입표준:지가술후3개월이상행관상동맥조영수방적관심병환자;배제표준:관상동맥조영현시원파병변관강직경협착＜50%화관상동맥조영수방시간＜3개월적관심병환자.입선환자년령(62±10)세,남92례,녀26례,소유환자균첨서지정동의서.근거미국심폐혈액협회적표준정의,장환자분위지가내재협착조여무재협착조,분별위68례화50례.방법:제취환자외주혈DNA,경PCR확증HO-1미위성서렬후채용Spreadex응효전영래진행기인분형.주요관찰지표:HO-1기인계동자미위성기인형빈솔급기여재협착적관계. 결과:휴대GT중복＜25차등위기인환자적재협착솔위47.5%,휴대량조GT중복균≥25차등위기인환자적재협착솔위68.4%(P＜0.05).경다원회귀분석교정관심병위험인소급개입치료적상관영향인소후,량조환자적재협착솔차이잉유현저성의의(OR=0.418,95%가신구간0.197～0.887,P＜0.05).결론:HO-1기인계동자미위성다태성여재협착상관,대관심병환자관상동맥지가치입술후적이급예방유십분중요적의의.
BACKGROUND: Heme oxygenase-1 (HO-1) promotor region has a pair of dinucleotide(guanosine thymidine, GT) repeats with a lengthy polymorphism, also named microsatellite polymorphism. Experiments in vitro have shown that we can indirectly learn about the level of gene transcription by measuring the number of GT repeats.OBJECTIVE: To investigate if an association exists between restenosis after percutaneous coronary intervention(PCI) and microsatellite polymorphism in HO-1 gene promoter.DESIGN: A case-control study based on the observation of the patients with coronary heart disease after undergoing coronary stenting.SETTING: Wards of the department of cardiology of a university hospital.PARTICIPANTS: A total of 118 patients were admitted from April 1996 to May 2002 at the Department of Cardiology of the First Hospital of Peking University who underwent successful coronary stenting. Inclusion criteria: The patients with coronary heart disease who underwent coronary stent implantation for more than 3 months now came to perform coronary angiography in follow-up. Exclusion criteria: Angiography showed that the stenosis of lumen in diameter in the patients with coronary heart disease was less than 50%and the follow-up in angiography was less than three months. There were 92males and 26 females aged(62±10) years old and the informed consents were obtained. The patients were divided into two groups according to the criteria stipulated by American Heart,Lung and Blood Association: in-stent restenosis(68 cases) and non-restenosis (50 cases).METHODS: DNA of the peripheral blood was isolated from the whole blood. The length of GT repeat was confirmed by PCR amplification and Spreadex Gel electrophoresis. Selected samples were sequenced with Sanger's method.MAIN OUTCOME MEASURES: Microsatellite gene frequency of HO-1promoter and its relationship with restenosis RESULTS: Patients with GT repeats <25 GT in the HO-1 gene promoter on either allele had significantly less often restenosis than patients without (47.5% vs. 68.4% ,P<0.05). After controlling some possible confound ing factorsfor coronary heart diseases, multivariate analysis indicated that still there was a significant difference between the two groups in restenosis rate(odd ratio 0. 418,95% CI: 0. 197 to 0. 887,P<0.05).CONCLUSION: The present study indicated that short(GT) n repeats of HO-1 gene promoter is associated with reduced post-PCI restenosis, which suggests the genetic contribution to in-stent restenosis after stent implantation. It may have important meanings to prevent the occurrence of restenosis.