儿童β2-肾上腺素能受体基因多态性与哮喘及吸入治疗疗效的关系

摘要

Objective To investigate the influence of genetic polymorphisms within β2-adrenoceptor ( β2-A R) gene on the development of childhood asthma and the clinical outcomes of the individual response to long-acting p2-agonist (LABA) therapy in Chinese Han children. Methods Argl6Gly, Glu27Gln and Thrl64Ile polymorphisms were detected within β2-adrenoceptor {β2-AR) in 212 children with asthma as well as in 52 normal subjects by DNA direct sequencing. And the relationship between polymorphisms and asthma was analyzed. A prospective pharmacogenetic study was carried out on selected 89 children with moderate persistent asthma aged between 5 and 11 years (mean age 7.57 ± 2.26 years). These children were given Salmeterol (Seretide) by inhalation for 12 weeks and lung function was tested before and after treatment. The influence of β2AR polymorphisms on children's lung function before and after inhalation of LABA was analyzed. Results The frequencies of both of Argl6Gly G and Glu27Gln G allele in asthma patients were significantly higher than those in the control group (38.7% vs. 31.7%, P < 0.01 and 7.1% vs. 0, P < 0.01 respectively). There was no significant difference of 164 allele polymorphisms between asthmatics and normal subjects (P > 0.05). After treatment 69.66% patients' conditions were within control and the lung function was significantly improved in FEV, (forced expiratory volume in 1 second) , FVC (forced vital capacity) , PEF (peak expiratory flow) and FEF25 50 75 (Forced expiratory flow between 25% and 75% of vital capacity). There was no difference among the three Argl6Gly groups and also that three Glu27Gln groups in clinical symptom control (P > 0.05). Conclusions β2 AR Argl6Gly G and Glu27Gln G but Thrl64Ile are statistically related with the development of childhood asthma. Itshows that no pharmacogenetic effect of β2-A R variation on therapeutic response to LABA in childhood asthma.%目的 探讨汉族儿童中β2-肾上腺素能受体(β2-AR)基因多态性对哮喘儿童发病和对长效β2受体激动剂(LABA)吸入疗效的影响.方法 采用DNA直接测序法,分别检测212例哮喘儿童和52例健康体检儿童的β2-AR的16位点、27位点和164位点的基因多态性分布,分析基因多态性和哮喘发病的关系.筛选其中5～11岁共89例中度持续性哮喘儿童,采用前瞻性的药物基因学研究,予以吸入沙美特罗替卡松干粉剂治疗12周,并于治疗前后分别进行常规通气肺功能检测,分析β2-AR基因多态性对哮喘儿童吸入LABA后肺功能的影响.结果 哮喘组Arg16Gly中具有G等位基因的频率高于正常对照组(分别为38.7％和31.7％,P＜0.01).哮喘组Gln27Glu中具有G等位基因的频率高于正常对照组(分别为7.1％和0,P＜0.01).164位点基因的多态性在哮喘组和正常对照组差异无统计学意义(P＞0.05).治疗后,哮喘儿童的控制率为69.66％,肺功能明显好转,第1秒用力呼出气量(FEV1),用力肺活量(FVC),呼气峰流速(PEF),呼出25％、50％、75％肺活量时的呼气流速(FEF25、50、75)均有明显改善.结论 16位点和27位点的多态性可能和汉族儿童哮喘发病有关；β2-AR基因164位点的基因多态性和哮喘无关,β2-AR基因16位点和27位点的多态性不影响哮喘患儿LABA治疗的疗效.