诱导型一氧化氮合酶和髓过氧化物酶基因多态性与肝炎后肝硬化合并肝肺综合征的相关性研究  

Gene polymorphism of inducible nitric oxide synthase and myeloperoxidase correlate with posthepatitic cirrhosis combined with hepatopulmonary syndrome

作　　者：戚秋藤[1] 王燕颖[1] 王文多[1] 张艳霞[1] 赵欣[1] 

机构地区：[1]黑龙江省医院消化内科,哈尔滨150036

出　　处：《中华实验和临床感染病杂志（电子版）》2011年第3期20-24,共5页Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition)

基　　金：黑龙江省科技攻关项目(GB07C32506)

摘　　要：目的探讨诱导型一氧化氮合酶(iNOS)和髓过氧化物酶(MPO)表达的基因多态性与肝炎后肝硬化肝肺综合征(HPS)易感性的关系。方法以63例肝炎后肝硬化HPS患者为病例组,182例非HPS患者为病例对照组,检测两组患者腹水沉渣包埋细胞块中iNOS和MPO的表达;以35例无肝病者为正常对照组,应用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术检测3组中iNOS Ser608Leu和MPO463位点的多态性。结果病例组中有杵状指41例(65.1%),蜘蛛痣49例(77.8%),食管静脉曲张(EV)51例(81.0%),腹水细胞块中MPO和iNOS表达阳性率和高表达率分别为100%,92.7%vs97.6%,75.6%;100%,71.4%vs100%,75.6%;98.0%,68.7%vs100%,75.6%。iNOS608核苷酸位点CC、CT和TT基因型在病例组和病例对照组的分布频率分别为81.0%、19.0%、0%和57.1%、40.0%、2.9%(P<0.05);MPO463核苷酸位点GG、GA和AA基因型在两组间的分布频率分别为76.2%、22.2%、1.6%和51.4%、42.9%、5.7%(P<0.05)。iNOS608和MPO463核苷酸位点多态性与HPS患病遗传易感性间有相互促进作用,同质性检验不同层间存在显著差异(P<0.01)。结论 iNOS和MPO表达与HPS临床表现具有一定的相关性,iN-OS基因608位点16外显子C→T突变可能是抵抗HPS发生和发展的因素,与MPO463G/A位点基因多态性在HPS发病的遗传易感因素中起协同作用。Objective To investigate whether the expression and gene polymorphism of inducible nitric oxide synthase （iNOS） and myeloperoxidase （MPO） are more susceptible to posthepatitic cirrhosis combined with hepatopulmonary syndrome （HPS）.Methods Expression of iNOS and MPO in 63 cases with posthepatitic cirrhosis combined with HPS and 182 cases with non-HPS were determined by examining cell blocks from ascites.Gene polymorphism of MPO 463 and iNOS Ser608Leu were determined by polymerase chain reaction and restriction fragment length polymorphism （PCR- RFLP） in 63 cases with HPS,182 cases with non-HPS and 35 cases with normal tissue.Results There were 41 cases with clubbing finger （65.1%）,49 cases with spider angioma （77.8%） and 51 cases with esophageal varices （EV） （81.0%） in HPS patients.The positive rates and expression rates of MPO and iNOS in cell blocks from ascites were 100%,92.7% vs 97.6%,75.6%;100%,71.4% vs 100%,75.6%;98.0%,68.7% vs 100%,75.6%,respectively.The prevalence rate of genotype CC,CT and TT in iNOS 608 nucleotide site were 81.0%,19.0%,0% in HPS patients and 57.1%,40.0%,2.9% in non-HPS patients （P 0.05）,respectively.The prevalence rate of genotype GG,GA,AA in MPO 463 nucleotide site were 76.2%,22.2%,1.6% and 51.4%,42.9%,5.7%,respectively （P 0.05）.Allele polymorphism of MPO 463 and iNOS 608 interacted on each other,with significant difference among different layers through homogeneity test （P 0.01）.Conclusions Clinical features of HPS correlated with the expressions of MPO and iNOS.C to T mutation on the 16th exon of iNOS gene might resist the development and progression of HPS,which may have synergetic effect with MPO 463 G/A gene polymorphism in genetic susceptibility of HPS.

关 键 词：肝肺综合征 诱导型一氧化氮合酶 髓过氧化物酶 多态性 单核苷酸 疾病遗传易 感性 

分 类 号：R575.2[医药卫生—消化系统]