HIF-1α基因多态性与iNOS表达在肝肺综合征中的临床意义  

Expression of iNOS and Hypoxia-inducible factor-1α gene polymorphism in hepatopulmonary syndrome

作　　者：王燕颖[1] 王文多[1] 张艳霞[1] 赵欣[1] 杨东亮[2] 

机构地区：[1]黑龙江省医院消化内科,黑龙江哈尔滨150036 [2]华中科技大学同济医学院附属同济医院

出　　处：《胃肠病学和肝病学杂志》2011年第1期81-85,共5页Chinese Journal of Gastroenterology and Hepatology

基　　金：黑龙江省科技攻关项目(GB07C32506)

摘　　要：目的探讨缺氧诱导因子-1α(HIF-1α)基因多态性和诱导型一氧化氮合酶(iNOS)蛋白表达与肝肺综合征(HPS)易感性的关系。方法对东北地区63例肝硬化HPS组和182例非HPS组,35例无肝病正常对照组,应用RFLP技术检测HIF-1α基因C1772T多态性与腹水沉渣包埋细胞块中iNOS表达的关系,并行遗传易感性分析。结果在非HPS组发现HIF-1α的CC、CT和TT三种基因型,分别为70.9%(129/182)、28.6%(52/182)、0.5%(1/182),对照组发现CC、CT两种基因型,分别为65.7%(23/35)、34.3%(12/35),两组比较无显著性差异(P>0.05);在HPS组发现CC、CT两种基因型,分别为92.1%(58/63)、7.9%(57/63),与前两组比较有显著性差异(P<0.05);对照组和非HPS组C等位基因频率分别为74.5%、77.4%,两组无显著性差异(P>0.05);而HPS组为92.6%,与前两组比较有显著性差异(P<0.05);而HPS组T等位基因频率为7.4%,与正常对照组25.5%和非HPS组22.6%相比差异有显著性(P<0.05);含有C等位基因(C/C、C/T)的病例,iNOS表达阳性率(55.42%)高于含有T等位基因(C/T、T/T)的病例(44.58%)(P<0.05)。结论 HIF-1α的CT多态性与肝硬化患者发生HPS遗传易感性相关;HIF-1α调节iNOS的表达,机体内HIF-1α与iNOS/NO系统的作用可能与HPS的发生发展相关。Objective To explore the relationship of the Hypoxia-inducible factor-1α（HIF-1α）-1772（C→T） polymorphism and the expression of inducible nitric oxide synthase（iNOS） in cirrhotic patients with hepatopulmonary syndrome（HPS）.Methods The enrolled subjects were divided into three groups according to their disease/health conditions： HPS group（cirrhotic patients with HPS;n=63）,non-HPS group（cirrhotic patients without HPS;n=182）,and the control group（healthy subjects without liver diseases;n=35）.The distribution of the HIF-1α-1772 C/T genotype and the expression of iNOS were detected by immunohistochemistry and polymerase chain reaction-restricted fragment length polymorphisms analysis.Results The CC,CT and TT were found in the non-HPS group,their prevalence rates were 70.9%（129/182）,28.6%（52/182）,0.5%（1/182） respectively;The CC and CT were found in the control group,their prevalence rates were 65.7%（23/35）,34.3%（12/35） respectively;the difference was not significant between the non-HPS group and control group（P0.05）.The CC and CT were found in the HPS group,their prevalence rates were 92.1%（58/63）,7.9%（5/63） respectively;the difference was significant compared with the non-HPS group and control group（P0.05）.The frequencies of the C allele in the control group and non-HPS group were 24.5%,77.4%,the difference was not significant（P0.05）.It was 92.6% in the HPS group,the difference was significant compared with non-HPS group and control group（P0.05）.The frequencies of the T allele in the control group and non-HPS group were 25.5%,22.6%,the difference was not significant（P0.05）.It was 7.4% in the HPS group,the difference was significant compared with non-HPS group and control group（P0.05）.The expression of iNOS was significantly higher in patients with the C allele than that in the T allele（55.42%,44.58%;P0.05）.Conclusion The HIF-1α-1772 C allele may increase the inducible expression of iNOS and be associated strongly with HPS.

关 键 词：肝肺综合征 缺氧诱导因子-1Α 多态性 诱导型一氧化氮合酶基因 

分 类 号：R575[医药卫生—消化系统]