Department of Allergy and Rheumatology, Ajou University School of Medicine, Suwon, Korea.
J Clin Pharm Ther. 2009 Dec;34(6):693-701. doi: 10.1111/j.1365-2710.2009.01054.x.
Inhaled corticosteroids (ICS) are widely used as maintenance regimens for asthma patients. However, response to ICS shows marked inter-individual variability. Genetic factors have been shown to be potential predictors of responsiveness to ICS. We aimed to evaluate those pharmacogenetic effects on asthma control in further detail.
Fifty-three mild-to-moderate asthmatics were genotyped for four genetic polymorphisms of four genes: beta2-adrenergic receptor (ADRB2), adenylate cyclase 9 (ADCY9), neurokinin receptor 2 (NK2R) and T-box 21 (TBX21). The principal clinical outcome was the achievement of asthma control, as assessed using the Global Initiative for Asthma (GINA) guidelines. During treatment with ICS, the forced expiratory volume in 1 second (FEV(1)), maximal mid-expiratory flow (MMEF) and peak expiratory flow rate (PEFR) were monitored every 4 weeks and twice daily.
Forty-eight of the 53 patients with asthma were in a controlled or partly controlled state after 12 weeks of treatment with ICS, whereas five asthmatics were in an uncontrolled state even after active treatment. Of the four genetic polymorphisms examined, NK2R G231E G>A and TBX21 H33Q C>G were significantly associated with asthma control status (P = 0.041 and P = 0.006). The subjects with wild-type alleles at each polymorphism showed a significant association with the well-controlled or partly controlled state, as compared to those with mutant alleles. At 5-12 weeks after ICS treatment, the NK2R G231E G>A was associated with therapeutic response to ICS, as reflected by improvement in predicted FEV(1)%.
Our results suggest that NK2R G231E G>A and TBX21 H33Q C>G are genetic predictors of response to ICS, at least with respect to asthma control status and changes in FEV(1)%, in Korean patients with asthma. Further prospective validation of those associations is necessary.
吸入性皮质类固醇（ICS）被广泛用作哮喘患者的维持治疗方案。然而，ICS 的反应表现出显著的个体间变异性。遗传因素已被证明是对 ICS 反应性的潜在预测因子。我们旨在更详细地评估这些药物遗传学效应对哮喘控制的影响。
对 53 名轻中度哮喘患者的四个基因的四个遗传多态性进行基因分型：β2-肾上腺素能受体（ADRB2）、腺苷酸环化酶 9（ADCY9）、神经激肽受体 2（NK2R）和 T 框 21（TBX21）。主要临床结局是使用全球哮喘倡议（GINA）指南评估的哮喘控制的实现。在 ICS 治疗期间，每 4 周和每天两次监测用力呼气量（FEV1）、最大中期呼气流速（MMEF）和呼气峰流量（PEFR）。
在接受 ICS 治疗 12 周后，53 名哮喘患者中有 48 名处于控制或部分控制状态，而 5 名哮喘患者即使在积极治疗后仍处于未控制状态。在所检查的四个遗传多态性中，NK2R G231E G>A 和 TBX21 H33Q C>G 与哮喘控制状态显著相关（P = 0.041 和 P = 0.006）。每个多态性的野生型等位基因的受试者与控制良好或部分控制状态显著相关，而突变型等位基因的受试者则不相关。在 ICS 治疗后 5-12 周，NK2R G231E G>A 与 ICS 的治疗反应相关，表现为预测 FEV1%的改善。
我们的结果表明，NK2R G231E G>A 和 TBX21 H33Q C>G 是韩国哮喘患者对 ICS 反应的遗传预测因子，至少与哮喘控制状态和 FEV1%的变化相关。需要进一步进行前瞻性验证这些关联。
