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目的:评价使用丙酸氟替卡松的哮喘患者,其β2-肾上腺素受体基因(ADRB2)Arg16Gly的变异对沙美特罗临床反应性的影响。方法:62例哮喘患者,给予丙酸氟替卡松/沙美特罗(FSC)(100μg/50μg),2次/天吸入,治疗12周,治疗结束后有2～4天的导出期;以DNA直接测序法,确定62例ADRB25个位点的基因型及单倍型。结果:①哮喘在沙美特罗治疗期间,无论Arg16Gly为哪一种基因型,哮喘控制指标如峰值呼气流速(PEF)、1秒钟用力呼气容积(FEV1)、沙丁胺醇的使用量以及哮喘症状评分较其基础值都有持续地明显地改善(P<0.001),Arg/Arg患者的PEF较其基础值增加了(114.4±21.5)L/min,Gly/Gly与Arg/Gly患者分别增加了(100.3±14.7)L/min和(103.3±23.7)L/min,但3种基因型的哮喘控制指标的变化的比较,差异无显著性(P>0.05);其他的3个哮喘指标也有相似的改变;②对沙美特罗的反应性不受单倍型配对的影响(P>0.05);③在导出期,所有患者的哮喘控制指标都有相似的下降,但无基因型方面的差异(P>0.05)。结论:在长期吸入糖皮质激素的情况下,Arg16Gly基因型或单倍型不会影响对沙美特罗的治疗反应性。然而,目前尚需要大规模的前瞻性的临床药物遗传学研究以及遗传流行病学研究来进一步阐明。
OBJECTIVE: To evaluate the effect of variation of Arg16Gly beta2-adrenergic receptor gene (ADRB2) on clinical response to salmeterol in asthma patients using fluticasone propionate. Methods: Sixty-two patients with asthma were given fluticasone / salmeterol (100μg / 50μg) propionate twice a day for 12 weeks after treatment. There were 2 to 4 days of induction period after the treatment was finished. DNA direct sequencing Method to determine the 62 ADRB25 loci genotypes and haplotypes. RESULTS: Asthma During the salmeterol treatment, regardless of the genotype of Arg16Gly, asthma control measures such as peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV1), amount of salbutamol, and asthma symptoms (P <0.001). PEF in patients with Arg / Arg increased by (114.4 ± 21.5) L / min compared with the baseline values, and Gly / Gly and Arg / Gly patients increased by (100.3 ± 14.7) L / min and (103.3 ± 23.7) L / min, respectively, but there was no significant difference in the changes of the three kinds of asthma control indicators (P> 0.05). The other three asthma indicators were also similar (2) The response to salmeterol was not affected by haplotype pairing (p> 0.05). In the lead-out phase, all patients had similar reduction in asthma control but no genotype differences P> 0.05). Conclusion: Arg16Gly genotype or haplotype did not affect the therapeutic response to salmeterol in the long-term inhaled corticosteroids. However, large-scale prospective clinical pharmacogenetics studies and genetic epidemiological studies are needed to further elucidate this.