青岛地区支气管哮喘患者TNF—α基因rsl800629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-I 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一哮喘病实验室,266000

出　　处：《国际呼吸杂志》2013年第3期165-169,共5页International Journal of Respiration

基　　金：基金项目：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rsl800629（－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TNpn基因rsl800629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rsl800629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-amRNA表达、TNFrd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，Pd0．01，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rsl800629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-α gene, plasma levels of TNF-α, ET-1 with bronchial asthma （asthma）. Methods The polymorphism in 65 asthmatic subjects and 50 healthy controls were determined by polymerase chain reaction restriction fragment of polymorphism （PCR-RFLP）. Expression of mRNA of TNF-α was tested by real-time PCR. The TNF-α, ET-1 levels were determined by ELISA. Results The statistical differences of the genotype frequency and allele frequency in TNF-α gene rs1800629 polymorphism were observed between asthma patients and healthy controls （ P =0. 048. P = 0. 023）. TNF-α mRNA expression and TNF-α, ET-1 levels were higher in asthma than control （P = 0. 001, P 〈0.01, P =0. 044）. TNF-α mRNA expression and TNF-α, ET-1 levels were higher in GA＋ AA than GG （ P =0. 012, P 〈0.01, P =0. 041）. There is positive correlation between TNF-α mRNA and plasma levels with ET-1 in 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-α gene has susceptibility to asthma,A allele is the predisposing gene of asthma, and can increase TNF-α expression 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：R562.25[医药卫生—呼吸系统]