Pharmacogenetics and Genomics 2015-07-01

Association between TAAR6 polymorphisms and airway responsiveness to inhaled corticosteroids in asthmatic patients.

Hun Soo Chang, Jeong-Seok Heo, Seung-Woo Shin, Da-Jeong Bae, Hyun Ji Song, Ji Ae Jun, Jeong Dong Kim, Jong-Sook Park, Byung Lae Park, Hyung Doo Shin, Choon-Sik Park

文献索引：Pharmacogenet. Genomics 25 , 334-42, (2015)

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摘要

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.