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

초록

Background 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 (% increment FEV1) 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. Methods The % increment FEV1 induced by 4 weeks' treatment with inhaled fluticasone propionate (1000 mu g daily) was measured in 246 asthmatics. The 15 SNPs of TAAR6 were genotyped using a TaqMan assay. An association analysis between % increment FEV1 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. Results Among the 15 SNPs and seven haplotypes of TAAR6, rs7772821 (T > G) on the 3 '-UTR showed the strongest correlation with inhaled corticosteroid-induced % increment FEV1 (P-corr=0.002 in the codominant model, P-corr=0.03 in the dominant model, P-corr=0.01 in the recessive model). The % increment FEV1 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). Conclusion The TAAR6 rs7772821 polymorphism may be one of the important genetic factors for predicting the response to treatment with inhaled corticosteroids in asthmatics.

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