Document Detail


Association between WDR21A polymorphisms and airway responsiveness to inhaled corticosteroids in asthmatic patients.
MedLine Citation:
PMID:  22366774     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: Genetic polymorphism is partially responsible for the wide variation in the response of moderate-to-severe asthmatic patients to inhaled corticosteroids. The goal of the study was to examine polymorphisms in WDR21A, which encodes a putative glucocorticoid receptor (GR)-interacting protein, for their possible association with corticosteroid responsiveness. METHODS: The change in forced expiratory volume in 1 s [FEV1 (ΔFEV1)] induced by 4 weeks of inhaled treatment with fluticasone propionate (1000 µg daily) was measured in 230 asthmatic patients. Fifteen single nucleotide polymorphisms (SNPs) of WDR21A were genotyped using a TaqMan assay, and 11 SNPs were used for further analysis. WDR21A transcripts were analyzed for variant splicing using reverse transcriptase-PCR. The WDR21A protein structure was predicted using a template-based modeling method and docked to a GR using Zdock. RESULTS: Of the 11 SNPs and three haplotypes of WDR21A analyzed, only the intronic SNP -10073G>C appeared to affect ΔFEV1. The ΔFEV1 of the -10073C/C homozygous genotype was twice that of the -10073G/G and -10073C/G genotypes (Pcorr=0.04 in recessive model). No splicing variant of WDR21A was observed, regardless of genotype. The predicted WDR21A protein structure was similar to the Gβ1 protein structure (template modeling-score=0.93). CONCLUSION: The minor allele -10073C of WDR21A may induce a good response to inhaled corticosteroids possibly through competition with the Gβ1 proteins for binding to GRs.
Authors:
Sung-Hwan Cho; Byung-Lae Park; Seung Woo Shin; Jeong-Seok Heo; Jong-Sook Park; Sung Woo Park; An-Soo Jang; Il Yup Chung; Houng-Doo Shin; Choon-Sik Park
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-24
Journal Detail:
Title:  Pharmacogenetics and genomics     Volume:  -     ISSN:  1744-6880     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101231005     Medline TA:  Pharmacogenet Genomics     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
aGenome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Wonmi-gu, Bucheon bDivision of Allergy and Respiratory Medicine, Department of Internal Medicine Soonchunhyang University Bucheon Hospital, Jung Dong, Wonmi Ku, Bucheon, Gyeonggi Do cDepartment of Genetic Epidemiology, SNP Genetics, Inc., Woolim Lion's Valley B, Gasan-dong, Geumcheon-Gu dDepartment of Life Science, Sogang University, Mapo-Gu, Seoul eCollege of Science and Technology, Hanyang University, Ansan, Kyunggi-Do, Korea.
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