Chang Hun Soo, Heo Jeong-Seok, Shin Seung-Woo, Bae Da-Jeong, Song Hyun Ji, Jun Ji Ae, Kim Jeong Dong, Park Jong-Sook, Park Byung Lae, Shin Hyung Doo, Park Choon-Sik
aDepartment of Medical Bioscience, Graduate School, Soonchunhyang University, Chungcheongnam-do bGenome Research Center, Division for Allergy and Respiratory Diseases cDepartment of Internal Medicine, Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, Gyeonggi Do dDepartment of Genetic Epidemiology, SNP Genetics Inc. eDepartment of Life Science, Sogang University, Seoul, Republic of Korea.
Pharmacogenet Genomics. 2015 Jul;25(7):334-42. doi: 10.1097/FPC.0000000000000141.
Genetic polymorphisms may be responsible for the wide variation in response to inhaled corticosteroids in asthmatic patients. We had previously reported that one polymorphism rs7772821, located on the 3'-UTR of trace amine-associated receptor 6 (TAAR6), is significantly associated with percentile changes in the forced expiratory volume in 1 s (%ΔFEV1) after inhaled corticosteroid treatment in asthmatics using a genome-wide association study. The aim of the present study was to validate the association between 15 single-nucleotide polymorphisms (SNPs) on the TAAR6 and airway responsiveness to inhaled corticosteroids in the asthmatics.
The %ΔFEV1 induced by 4 weeks' treatment with inhaled fluticasone propionate (1000 μg daily) was measured in 246 asthmatics. The 15 SNPs of TAAR6 were genotyped using a TaqMan assay. An association analysis between %ΔFEV1 and TAAR6 polymorphisms was carried out using a linear regression model controlling for age, sex, smoking status, presence of atopy, and baseline FEV1 as covariates.
Among the 15 SNPs and seven haplotypes of TAAR6, rs7772821 (T>G) on the 3'-UTR showed the strongest correlation with inhaled corticosteroid-induced %ΔFEV1 (Pcorr=0.002 in the codominant model, Pcorr=0.03 in the dominant model, Pcorr=0.01 in the recessive model). The %ΔFEV1 of the rs7772821T>G minor homozygotes (60.77%) was higher than that of patients harboring either the rs7772821 T/G or T/T genotypes (21.32 and 31.60%, respectively).
The TAAR6 rs7772821 polymorphism may be one of the important genetic factors for predicting the response to treatment with inhaled corticosteroids in asthmatics.
基因多态性可能是导致哮喘患者对吸入性糖皮质激素反应差异巨大的原因。我们之前曾报道，通过全基因组关联研究发现，位于痕量胺相关受体6（TAAR6）3'-UTR区域的一个基因多态性位点rs7772821，与哮喘患者吸入糖皮质激素治疗后1秒用力呼气量的百分比变化（%ΔFEV1）显著相关。本研究的目的是验证TAAR6上15个单核苷酸多态性（SNP）与哮喘患者气道对吸入糖皮质激素反应性之间的关联。
在246名哮喘患者中测量了吸入丙酸氟替卡松（每日1000μg）4周治疗所诱导的%ΔFEV1。使用TaqMan分析法对TAAR6的15个SNP进行基因分型。采用线性回归模型进行%ΔFEV1与TAAR6多态性之间的关联分析，将年龄、性别、吸烟状况、特应性状态和基线FEV1作为协变量进行控制。
在TAAR6的15个SNP和7个单倍型中，3'-UTR区域的rs7772821（T>G）与吸入糖皮质激素诱导的%ΔFEV1显示出最强的相关性（共显性模型中Pcorr = 0.002，显性模型中Pcorr = 0.03，隐性模型中Pcorr = 0.01）。rs7772821T>G次要纯合子的%ΔFEV1（60.77%）高于携带rs7772821 T/G或T/T基因型的患者（分别为21.32%和31.60%）。
TAAR6 rs7772821多态性可能是预测哮喘患者对吸入糖皮质激素治疗反应的重要遗传因素之一。
