β_2肾上腺素受体16,27位遗传多态性与哮喘关系研究

The Association of Polymorphisms in Position 16,27 of β_2- adrenergic Receptor with Asthma

目的 :探讨 β2 肾上腺素受体编码区 16 ,2 7位点遗传多态性与哮喘的关系 .方法 :通过测序确定15 4名受试者的基因突变类型 (正常对照组 86名 ,哮喘组 6 8名 ) ,并测定哮喘患者的FEV1,调查患者使用 β2激动剂情况 ,以分析哮喘与 16 ,2 7位点遗传多态性的关系 .结果 :中国人群存在 16位点Arg→Gly及 2 7位点Gln→Glu的突变 ,但与高加索人群比较突变频率较低 ,16位点分别为 42 31%和 70 0 % (P <0 0 0 1) .2 7位点分别为 8 7%和 49 1% (P <0 0 0 1) .16位点基因型分别为Arg/Arg ,Arg/Gly ,Gly/Gl的患者 ,FEV1分别为 0 6 4± 0 0 6 ,0 73± 0 0 4及 0 82± 0 0 5 (F =78 85 ,P <0 0 0 1) ,差异显著 .平均每周使用 β2 激动剂(1 7± 0 3) ,(3 8± 1 4)及 (6 5± 2 2 )mg (F =6 5 73,P <0 0 0 1) .结论 :中国西南地区人群与高加索人群 16 ,2 7位点的基因突变频率不同 ,β2 肾上腺素受体的遗传多态性不是哮喘发病的基本原因 。

Objective: To investigate the relation between asthma and polymorphism in 16 and 27 position of β 2-adrenergic receptor (β 2-AR). Methods: We genotyped 154 participants by sequencing. Among them, 86 were controls and 68 were asthmas. Spirometry was performed in 68 asthmas, and also their usage of β 2-agonist was investigated; the association of polymorphisms in 16 and 27 position of β 2-AR with asthma was analyzed. Results: There were a Arg→Gly mutation at β 2-AR-16 and Gln→Glu mutation at β 2-AR-27 in Chinese. But when compared with European, both the mutation frequency at the two positions were lower, the Arg→Gly was 70.0% and 42.31%(P<0.001); the Gln→Glu was 49.1% and 8.7%(P<0.001). In asthma, the patients who carried unlike β 2-AR-16 genotype (Arg/Arg, Arg/Gly, Gly/Gly) had a different FEV 1(0.63±0.06,0.72±0.04,0.84±0.05) and different usage of β 2-agonist inhaled respectively, the difference across the groups was significant (F=78.85, P<0.001, and F=65.73, P<0.001). Conclusions: The gene mutation frequency of β 2-AR-16 and 27 positions was different between Chinese and European; the genetic polymorphism of β 2-AR is not the primary cause of asthma, but it had an important effect on the severity of asthma.