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


METHODS
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.


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 %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).


CONCLUSIONS
The TAAR6 rs7772821 polymorphism may be one of the important genetic factors for predicting the response to treatment with inhaled corticosteroids in asthmatics.
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.
Hun Soo
HS
Chang
Jeong-Seok
JS
Heo
Seung-Woo
SW
Shin
Da-Jeong
DJ
Bae
Hyun Ji
HJ
Song
Ji Ae
JA
Jun
Jeong Dong
JD
Kim
Jong-Sook
JS
Park
Byung Lae
BL
Park
Hyung Doo
HD
Shin
Choon-Sik
CS
Park
D020413:3' Untranslated Regions; D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D000068298:Fluticasone / Q000008:administration & dosage; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D043562:Receptors, G-Protein-Coupled; D055815:Young Adult; D000095383:Trace Amine-Associated Receptors
D020413:3' Untranslated Regions; D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D018797:Cell Cycle Proteins; D000068298:Fluticasone; D009687:Nuclear Proteins; D043562:Receptors, G-Protein-Coupled; C493988:TAAR6 protein, human; D000095383:Trace Amine-Associated Receptors