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-lα (HIF-lα) -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-lα-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 ( P ＞ 0.05 ). 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 (P ＜ 0.05). The frequencies of the C allele in the control group and non-HPS group were 24.5％ , 77.4％ , the difference was not significant (P ＞ 0.05). It was 92.6％ in the HPS group, the difference was significant compared with non-HPS group and control group (P ＜ 0.05 ). The frequencies of the T allele in the control group and non-HPS group were 25.5％ , 22.6％ , the difference was not significant (P ＞0.05 ) . It was 7.4％ in the HPS group, the difference was significant compared with non-HPS group and control group (P ＜ 0.05 ). The expression of iNOS was significantly higher in patients with the C allele than that in the T allele (55.42％ , 44.58％; P ＜ 0.05 ). Conclusion The HIF-1 α-1772 C allele may increase the inducible expression of iNOS and be associated strongly with HPS.
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