青岛地区支气管哮喘患者TNF-α基因rs1800629位点多态性与表达及TNF-α、内皮素水平相关研究  

Single nucleotide polymorphism and expression of TNF-α , plasma levels of TNF-α , ET-1 in bronchial asthma

作　　者：李莹[1,2] 纪霞 王海燕 贾少丹 

机构地区：[1]潍坊医学院,261000 [2]青岛市常见病重点实验室-哮喘病实验室,266000

出　　处：《中华哮喘杂志（电子版）》2013年第2期89-94,共6页Chinese Journal of Asthma(Electronic Version)

基　　金：青岛市市南区科技发展计划项目(2009-4-31-GG);山东省医药卫生科技发展计划项目(2009-17);青岛市科技计划基础研究项目任务书(2009-11-2-4-7-(2)-jch)

摘　　要：目的探讨青岛地区支气管哮喘(简称哮喘)患者肿瘤坏死因子α(TNF-α)基因启动子区域rs1800629(-308)位点G/A单核苷酸多态性与表达及血浆TNF-α、内皮素1(ET-1)的水平。方法应用限制性片段长度多态性聚合酶链反应(PCR-RFLP)检测65例哮喘患者与50例健康者TNF-α基因rs1800629位点G/A单核苷酸多态性,荧光定量PCR检测外周血单个核细胞TNF-αmRNA表达,ELISA测定其TNF-α、ET-1水平。结果哮喘组和对照组TNF-α基因rs1800629位点基因型及等位基因频率差异有统计学意义(P=0.048;P=0.023)。哮喘组与对照组相比,TNF-αmRNA表达、TNF-α及ET-1浓度差异有统计学意义(P=0.001,P<0.01,P=0.044)。哮喘组GA+AA组与GG组相比,TNF-αmRNA表达、TNF-α及ET-1浓度差异有统计学意义(P=0.012,P<0.01,P=0.041)。哮喘组ET-1与TNF-αmRNA表达及浓度分别呈正相关(r=0.607,P<0.05;r=0.658,P<0.01)。结论 TNF-α基因启动子区rs1800629位点G/A多态性与哮喘的易感性有相关性,A等位基因为哮喘易感基因,并且可以增加TNF-α表达及TNF-α、ET-1含量。TNF-α、ET-1可能参与哮喘患者气道炎症反应,且在哮喘发病时具有相互作用。Objective To investigate the correlation between the single nucleotide polymorphism ( SNP ) of rs1800629 ( -308 ) G / A site and expression of TNF-αgene , plasma levels of TNF-α , ET-1with bronchial asthma ( asthma ) .Methods The polymorphism in 65asthmatic subjects and 50healthy controls were determined by polymerase chain reaction restriction fragment of polymorphism ( PCR-RFLP ) . Expression of mRNA of TNF-αwas tested by real-time PCR.The TNF-α , ET-1levels were determined by ELISA.Results The statistical differences of the genotype frequency and allele frequency in TNF-αgene rs1800629polymorphism were observed between asthma patients and healthy controls ( P =0.048.P =0.023 ) .TNF-αmRNA expression and TNF-α , ET-1levels were higher in asthma than control ( P =0.001 , P <0.01 , P =0.044 ) .TNF-αmRNA expression and TNF-α , ET-1levels were higher in GA+ AA than GG ( P =0.012 , P <0.01 , P =0.041 ) .There is positive correlation between TNF-αmRNA and plasma levels with ET-1in asthma ( r=0.607 , P <0.05.r=0.658 , P <0.01 ) .Conclusions The polymorphism of rs1800629 ( -308 ) G / A site in the promoter region of TNF-αgene has susceptibility to asthma , A allele is the predisposing gene of asthma , and can increase TNF-αexpression and serum TNF-α , ET-1.TNF-α , ET-1 may has certain effect in asthma airway inflammation , these two cytokine may have interaction effect.

关 键 词：哮喘 肿瘤坏死因子Α 内皮素1 单核苷酸多态性 荧光定量PCR 

分 类 号：X51[环境科学与工程—环境工程] TU4[建筑科学—土工工程]