β_2肾上腺素受体基因编码区变异对儿童重度哮喘患者ICS/LABAs联合治疗反应性影响

Effect of gene polymorphisms in ADRB2 coding region on response to ICS / LABAs combination treatment in Chinese Han children with severe asthma

目的:探讨汉族人群β2肾上腺素受体(ADRB2)基因编码区多态性对糖皮质激素和长效β2受体激动剂(ICS/LABAs)联合治疗儿童重度支气管哮喘患者反应的影响。方法:研究设计采用前瞻性的药物基因学研究,83例重度儿童持续性哮喘,采用PCR-RFLP方法对ADRB2基因编码区Arg16Gly和Gln27Glu两个常见多态性位点进行基因分型,随后予以ICS(丙酸氟替卡松100μg)加LABA(沙美特罗25μg),每天2次吸入给药治疗16周。治疗前后分别进行肺功能检测。分析ADRB2基因编码区多态性对哮喘患儿哮喘控制率、急性发作、沙丁胺醇使用次数及肺功能的影响。结果:ADRB2基因第16位氨基酸3个基因型(Arg/Arg,Arg/Gly和Gly/Gly)和第27位氨基酸的3个基因型(Gln/Gln,Gln/Glu和Glu/Glu)在患者年龄、性别、Ig E水平和嗜酸性粒细胞水平无统计学差异(P<0.05)。治疗后,不同基因型患者的哮喘症状得到良好的控制(完全控制率达73.5%)以及肺功能指标(FEV1,FVC,PEF)比基线均有明显的改善(P<0.05)。不同基因型对哮喘患儿的控制率、治疗期间急性发作数、沙丁胺醇的使用量及肺功能指标改善无明显的差异(P>0.05)。第16位氨基酸和第27位氨基酸位点构建的3种常见单倍型(Arg/Arg-Gln/Gln,Gly/Gly-Gln/Gln和Gly/Gly-Glu/Glu)与哮喘患儿的控制率、治疗期间急性发作、沙丁胺醇的使用及肺功能指标也无关联。结论:ADRB2基因编码区多态性不影响汉族儿童重度哮喘应用ICS/LABAs联合治疗的反应性。

AIM： To determine the influence of ADRB2 polymorphisms on response to inhale ICS and LABAs regularly in Chinese Han children with severe asthma. METHODS： This pharmacogenetic study is a population-based prospective cohort study.Two common polymorphisms of ADRB2 at codons 16 and 27 were genotyped using PCR-RFLP method in83 children with severe asthma receiving ICS（ fluticasone propionate 100 μg） plus LABA（ Salmeterol25 μg）,2 times everyday for 16 weeks. Lung function was tested before and after treatment. The influence of ADRB2 polymorphisms on the rate of children asthma control,the number of exacerbations,salbutamol use and lung function changed before and after treatment were analyzed. RESULTS： No significant differences were found related to sex,age,Ig E levels,and number of blood eosinophils among the 3genotypes Arg / Arg,Arg / Gly and Gly / Gly at 16 loci and 3 genotypes Gln / Gln,Gln / Glu and Glu / Glu at27 loci at baseline. After treatment 73. 5% patient＇s clinical outcome was in control and the lung function was significantly improved in FEV1,FVC,and PEF.However,there was no significant difference across different ADRB2 genotypes in asthma control rate,number of exacerbation,salbutamol use and lung function improvement（ FEV1,FVC,PEF）. There was also no significant difference among 3 common haplotypes Arg / Arg-Gln / Gln,Gly / Gly-Gln / Gln and Gly / Gly-Glu / Glu constructed by 16 loci and 27 loci in asthma control rate,number of exacerbation,salbutamol use and lung function improvement. CONCLUSION： ADRB2 gene polymorphisms are not associated with therapeutic response to ICS / LABA in Anhui Han nationality childhood severe asthma.