PAI-1基因多态性对哮喘气道重塑影响的研究  

Role of 4 G/5 G polymorphism of PAI-1 gene in airway remodeling

作　　者：张晓岩[1] 林江涛[1] 杨萌[1] 何洁[1] 黄小杰[2] 蔡哲[2] 张岚[2] 舒峻[2] 

机构地区：[1]卫生部中日友好医院呼吸内科,北京100029 [2]卫生部中日友好医院临床医学研究所免疫室,北京100029

出　　处：《实用临床医药杂志》2009年第12期1-6,共6页Journal of Clinical Medicine in Practice

基　　金：北京市自然科学基金资助项目(7063092)

摘　　要：目的探讨纤溶酶原激活物抑制剂-1(PAI-1)基因启动子-675 4G/5G多态性对哮喘气道重塑的影响。方法慢性持续期哮喘患者(30例)和健康人(20名)分列为轻度哮喘组、中重度哮喘组和健康人组,用等位基因特异性PCR(ASO)法测定PAI-1启动子区域-675位点多态性,ELISA法测定血浆PAI-1、TGF-β1和MMP-9水平,高分辨率CT(HRCT)观察所有受试者肺部影像学特征,运用PickerPQ6000分析软件测定气道壁厚度(T)、气道壁面积(WA),采用气道壁厚度/气道外径(T/D)和气道壁面积占气道总面积百分比(WA%)作为标化指标。结果PAI-1的4 G/4 G、4 G/5 G和5 G/5 G 3种基因型表达的TGF-β1、T和WA%差异有统计学意义(P<0.05)。血浆PAI-1仅与血浆TGF-β1存在相关关系(r=0.335,P<0.05),与T、T/D、WA和WA%无相关关系(P>0.05)。多元方差分析显示PAI-1基因多态性、血浆TGF-β1、血浆PAI-1水平与PAI-14G/5 G基因多态性的交互作用对气道重塑表型的影响有统计学意义(P=0.050,P=0.026,P=0.030)。结论PAI-1启动子4 G/5 G多态性可能是哮喘气道重塑的独立影响因素。Objective To explore the possible role of-675 4 G/5 G PAI-1 polymorphism in asthmatic remodeling.Methods Genomic DNA was isolated from the peripheral blood of 30 chronic persistent asthmatics and 20 healthy subjects for 3 groups.The PAI-1 4 G/5 G genotypes were determined by an allele-specific polymerase chain reaction.Everyone performed HRCT for the evaluation of the severity of asthma and airway remodeling.Quantitative assessment was used to analyze the thickness of airway wall（T,T/D） and airway wall area（WA,WA%）.Levels of PAI-1,TGF-β1 and MMP-9 in plasma were detected by ELISA.Results Levels of TGF-β1,T and WA% for 4 G/4 G genotype of PAI-1 were significantly higher than those of 4 G/5 G and 5 G/5 G genotype（P〈0.05）.Morning plasma PAI-1 concentration was correlated significantly with TGF-β1（r=0.335,P〈0.05）,but not with T,T/D,WA and WA%（P〉0.05）.Multivariate analysis of variance using T,T/D,WA,WA% as dependent variables and age,gender,group,index of smoking,course of disease,PAI-1 gene polymorphism,plasma PAI-1,TGF-β1 and plasma MMP-9 as the independent variables,revealed a significant effect of plasma PAI-1 and PAI-1 gene polymorphism（P〈0.05）.The PAI-1 gene polymorphism is one of the important factors of airway remodeling（P=0.050）.Conclusions PAI-1 4 G/5 G polymorphism may be one of main factors of airway remodeling.

关 键 词：纤溶酶原激活物抑制剂-1 基因多态性 气道重塑 高分辨率CT 

分 类 号：R562.2[医药卫生—呼吸系统]