科研之友
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摘要
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.
- 出版日期2015-7
