ADRB2基因多态性/单倍型与中国南方汉族人群支气管哮喘相关表型的关系  

Association between polymorphisms/haplotypes of ADRB2 gene and asthma-related phenotypes in a South Chinese Han population

作　　者：陈慧芬[1] 邱玉英[2] 

机构地区：[1]南京医科大学鼓楼临床学院呼吸科,210008 [2]南京大学医学院附属鼓楼医院呼吸科,210008

出　　处：《国际呼吸杂志》2015年第7期485-491,共7页International Journal of Respiration

基　　金：南京市卫生局卫生青年人才培养工程（第一层次）资助

摘　　要：目的 研究中国南方汉族人群β2肾上腺素能受体（ADRB2）基因单核苷酸多态性/单倍型与支气管哮喘（简称哮喘）相关表型的相关性.方法 采用Taqman探针法对379例哮喘患者和435例健康对照者ADRB2基因6个位点（T-2387C、5＇LC Arg19 Cys、Arg16Gly、Glu27Gln、Thr164Ile和C523A）进行基因分型,并确定其单倍型.采用酶联免疫吸附（enzyme linked immunosorbent assay,ELISA）法检测血清总IgE.结果 164位均为野生型纯合基因型,未检测到突变型等位基因,未纳入统计分析.T-2387C、5＇LC Arg19 Cys、Arg16Gly、Glu27Gln和C523A基因型频率和单倍型频率在轻＋中度哮喘组与重度哮喘组间分布差异均无统计学意义（x2分别为：2.45,4.12,0.43,5.81,0.44;2.39,0.80,1.42,0.20,P值均＞0.05）,在夜间哮喘组与非夜间哮喘组间分布差异亦无统计学意义（x2分别为：0.77,1.51,1.68,1.51,1.03;1.05,0.45,1.01,0.40,P值均＞0.05）.哮喘组血清总IgE[（83.95±67.35） μg/L]高于正常健康组[（66.12±61.27）μg/L）],各位点基因型间血清总IgE水平比较差异无统计学意义（x2或Z值分别为：1.88,-1.21,1.677,-1.17,1.93,P值均＞0.05）,5个位点组成的4种纯合型单倍型间血清总IgE水平比较差异亦无统计学意义（x2为1.33,P＞0.05）.同种基因型的哮喘患者血清总IgE水平与哮喘病情严重程度及夜间哮喘差异均无统计学意义（Z值分别为：-0.73,-0.06,-0.64,-1.35,-1.82,-1.15,-0.05,-1.15,-1.37,-1.78,-0.44,-0.01,-0.35;-1.48,-0.93,-0.45,-0.42,-0.48,-0.11,-0.09,-0.80,-0.27,-0.26,-0.30,-0.23,-1.03,P值均＞0.05）.但将不同严重程度哮喘组分层分析发现,重度哮喘组Arg/Cys19＋Cys/Cys19、Gln/Glu27＋Glu/Glu27有更高的血清IgE水平.结论 ADRB2基因单核苷酸多态性/单倍型与哮喘严重程度、夜间哮喘无显著相关性,但-47、79位可能与重度哮喘患者血清总IgE有关.Objective The aim of this study was to evaluate the potential relationship between polymorphisms/haplotypes of β2-adrenergic receptor （ADRB2） gene and asthma-related phenotypes.Methods Six polymorphisms loci （T-2387C,5＇ LC Arg19 Cys,Arg16Gly,Glu27Gln,Thr164Ile and C523A） of the ADRB2 gene were genotyped by the TaqMan assay in 379 asthmatics and 435 healthy controls,the haplotypes also be analyzed.Total serum IgE level was measured by enzyme linked immunosorbent assay （ELISA）.Results The mutant allele at 164 loci was not observed and only the homozygous wild-type was found in both asthmatic patients and control subjects,therefore it was not included in the statistical analysis.There were significant difference in both genotype frequencies and haplotype frequencies distribution of T-2387C,5＇LC Arg19 Cys,Arg16Gly,Glu27Gln and C523A between asthmatic patients and control subjects （x2 were 2.45,4.12,0.43,5.81,0.44;2.39,0.80,1.42,0.20respectly,all P 〉0.05）,and so were between the nocturnal asthma and non-nocturnal asthma （x2 were：0.77,1.51,1.68,1.51,1.03;1.05,0.45,1.01,0.40 respectly,all P 〉0.05）.Total serum IgE levels in asthma group [（83.95±67.35） μg/L] was higher than normal subjects [（66.12±61.27） μtg/L] but there was no significant difference in total serum IgE levels between all genotypes in the five loci （all P 〉0.05）.No association was found in relation to the serum levels of IgE between the four homozygous haplotypes accroding to five loci.But we found the individual who carring the Arg/Cys19 ＋ Cys/Cys19,Gln/Glu27＋Glu/Glu27 genotype in severe asthma had higher level of IgE values according to asthma severity.Conclusions There were no association between polymorphisms/haplotype of ADRB2 and asthma severity and nocturnal asthma,but we found that there might be asociation between-47,79 loci and the IgE values in severe asthma.

关 键 词：哮喘 ADRB2基因 多态性/单倍型 表型 

分 类 号：R562.25[医药卫生—呼吸系统]