血红素氧化酶1基因多态和冠状动脉旁路移植后的炎症反应  

Heme-oxygenase promoter microsatellite polymorphism and inflammatory response to coronary artery bypass surgery

作　　者：李萍[1] Jules Sanders Emma Hawe David Brull Jutta Palmen Jayshree Achary Hugh Montgomery Steve E.Humphries 

机构地区：[1]南昌大学第二附属医院心血管内科,江西省南昌市330006 [2]英国伦敦大学学院心血管遗传病学中心

出　　处：《中国组织工程研究与临床康复》2009年第22期4261-4265,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：江西省科技支撑计划项目"HO-1基因启动子GT序列对冠脉支架术炎症及再狭窄的影响"资助

摘　　要：背景:血红素氧化酶1是降解血红素生成胆红素、亚铁及一氧化碳过程的限速酶,具有重要的抗炎功能,其启动子部位GT重复序列的多态性可使该基因表达的水平不同,重复序列较短者基因转录活性较高。目的:观察冠状动脉旁路移植术后炎性标记物白细胞介素6,C-反应蛋白及纤维蛋白原的水平及其相关性,探讨血红素氧化酶1基因变量对它们的影响。设计、时间及地点:观察性试验,于2003年在英国伦敦大学学院心血管遗传病学中心完成。对象:220例符合入选条件的行冠状动脉旁路移植术的患者,男179例,女41例,年龄(63.34±9.64)岁。方法:PCR方法和DNA测序仪分析其血红素氧化酶1基因启动子部位GT重复序列的长短;于手术前及术后6,24,48,72,96,120h分别测白细胞介素6、C-反应蛋白和纤维蛋白原水平。主要观察指标:血红素氧化酶1基因启动子部位GT重复序列的长短;手术前及术后不同时间白细胞介素6、C-反应蛋白和纤维蛋白原水平。结果:术前白细胞介素6水平与C-反应蛋白及纤维蛋白原值显著相关(r=0.48,P<0.0001;r=0.41,P<0.0001),术后3者均显著升高,白细胞介素6峰质量浓度与C-反应蛋白峰质量浓度显著相关(r=0.34,P=0.0009),但与纤维蛋白原峰值无明显相关性(r=0.15,P=0.13)。术前C-反应蛋白值在血红素氧化酶1各基因组间存在明显差异,长GT重复序列者比短GT重复序列携带者高[(3.76±0.79),(2.07±0.17)mg/L,P=0.013];术后则各基因型组间水平相似。结论:炎症标志物的水平间存在相关性,血红素氧化酶1基因多态只与术前的基础C-反应蛋白和纤维蛋白原值有关,提示其可能只影响疾病的慢性炎症状态,从而影响炎性疾病的发生,而非急性炎症反应。BACKGROUND： Heme-oxygenase 1 （HO-1） is a rate-limiting enzyme in the degradation of heme to bilirubin, ferritin and carbon monoxide and may have significant anti-inflammatory function. The HO-1 gene promoter region shows microsatellite polymorphism with different （GT）n repeats, with short allele associated with high gene expression. OBJECTIVE： To explore levels of interleukin-6 （IL-6）, C-reactive protein {CRP） and fibrinogen and their relationship to HO-1 genotype following coronary artery bypass surgery, and examined the influence of HO-1 genic variance. DESIGN, TIME AND SETTING： Observation experiment. The study was performed at the Cardiovascular Genetics Center, University College London in 2003. PARTICIPANTS： 220 patients underwent coronary artery bypass surgery, including 179 males, and 41 females, aged （63.34±9.64） years. METHODS： The patients were genotyped for the HO-1 promoter polymorphism using PCR and automated DNA capillary sequencer. IL-6, CRP and fibrinogen were measured before and 6, 24, 48, 72, 96 and 120 hours after coronary artery bypass surgery. MAIN OUTCOME MEASURES： Length of （GT）n repeats of HO-1 gene promoter region; IL-6, CRP and fibrinogen levels before and after surgery. RESULTS： Before surgery IL-6 levels showed a strong correlation with CRP and fibrinogen （r=0.48, P 〈 0.000 1 ; r=0.41, P 〈 0.000 1）. All three acute phase reactants showed a significant increase after surgery; peak IL-6 was strongly correlated with peak CRP （r=0.34, P=0.000 9）, but not with peak fibrinogen （r=0.15, P=0.13）; Baseline CRP differed by genotype： those carrying at least one long allele had higher CRP than those with no long altete [（3.76±0.79）, （2.07±0.17） mulL, P=-0.0131, but the levels were similar following surgery. CONCLUSION： There is a strong correlation between the measured acute phase reactants. There is only an association between the HO-1 microsatellite polymorphism and CRP and fibrinogen levels at baseline, indicating

关 键 词：血红素氧化酶1 基因多态 炎症反应 冠状动脉旁路移植术 

分 类 号：R654.2[医药卫生—外科学]