摘要目的 探讨ADRB2基因rs1042713和rs1042714位点多态性与儿童支气管哮喘(哮喘)易感的相关性及对治疗的反应性,并初步了解其机制.方法 收集2014年8月至2016年4月在郑州儿童医院门诊及住院确诊的哮喘病例组(173例)和健康对照组(166例)儿童的口腔上皮细胞,采用Taqman探针实时荧光定量检测儿童ADRB2基因编码区rs1042713和rs1042714位点的基因型,比较2组基因型分布的差异;比较哮喘病例组不同基因型患儿的治疗疗效,而后采用生物信息学分析ADRB2不同基因型对应的氨基酸序列、蛋白结构的差异.结果 哮喘病例组和健康对照组rs1042713位点的基因型及等位基因频率分布比较差异均有统计学意义(P=0.001、0.000),rs1042714位点比较差异无统计学意义(P=0.159、0.061).rs1042713位点GG基因型患者需要的用药剂量与AA、AG基因型患者比较差异有统计学意义(H=12.583,P=0.002),但rs1042714位点各个基因型对药物的反应性比较差异无统计学意义(H=2.696,P=0.260).rs1042713位点的多态性引起蛋白局部结构的不同,rs1042714位点的多态性对应的蛋白结构无差异.结论 ADRB2基因s1042713位点多态性不仅与儿童哮喘的易感相关,也在一定程度上影响哮喘对治疗的反应性,而rs1042714位点多态性与哮喘易感性和治疗反应性均不相关,其机制可能与不同基因型对应的蛋白结构及功能差异有关.

abstractsObjective To discuss the association between ADRB2 gene polymorphism of rs1042713, rs1042714 locus and susceptibility of childhood bronchial asthma and response to the treatment,and to understant the preliminary pathogenesis of asthma preliminary. Methods The oral epithelial cells of children in asthma case group from the outpatient or inpatients at the Zhengzhou Children′s Hospital (173 cases)and healthy control group (166 ca-ses)were collec-ted. The genotypes of ADRB2 gene encoding area rs1042713 locus and rs1042714 were tested by the mean of Taqman probe real-time fluorescent quantitative PCR,and the difference was analyzed. The therapeutic effects between 2 groups were compared,and then the differences in the amino acid sequence and protein structure correspon-ding genotypes of ADRB2 genes were investigated by using bioinformatics analysis. Results There were statistical differences in genotype frequency and allele frequency of rs1042713 locus between asthma case group and healthy con-trol group(P = 0. 001,0. 000),but no difference at rs1042714 locus(P = 0. 159,0. 061). GG genotype of rs1042713 locus had significant differences in adjusting the drug dosage with AA,AG genotype patients(H = 12. 583,P = 0. 002), but the different genotype of rs1042714 locus had no significant differences in adjusting the drug dosage(H = 2. 696, P = 0. 260). The polymorphism of rs1042713 locus caused protein local structure changes,but the homologous protein structure of rs1042714 locus caused no changes. Conclusions ADRB2 gene polymorphism of rs1042713 locus is not only associated with the susceptibility of childhood bronchial asthma,but also has an effect on β2-receptor agonist treatment to a certain extent. But polymorphism of rs1042714 locus may not be associated with the susceptibility of asth-ma and the response to treatment. The reason may be different genotypes leading to different protein structures and bio-logical functions. The mechanism may be related to the structural and functional differences of protein structures corre-sponding to different genotypes.