Association between WDR21A polymorphisms and airway responsiveness to inhaled corticosteroids in asthmatic patients
- Authors
- Cho, Sung-Hwan; Park, Byung-Lae; Shin, Seung Woo; Heo, Jeong-Seok; Park, Jong-Sook; Park, Sung Woo; Jang, An-Soo; Chung, Il Yup; Shin, Houng-Doo; Park, Choon-Sik
- Issue Date
- May-2012
- Publisher
- Lippincott Williams & Wilkins Ltd.
- Keywords
- asthma; corticosteroid; G-protein beta subunit; G-protein gamma subunit; pharmacogenetics; single nucleotide polymorphism; WDR21A
- Citation
- Pharmacogenetics and Genomics, v.22, no.5, pp 327 - 335
- Pages
- 9
- Journal Title
- Pharmacogenetics and Genomics
- Volume
- 22
- Number
- 5
- Start Page
- 327
- End Page
- 335
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/15232
- DOI
- 10.1097/FPC.0b013e32834ef849
- ISSN
- 1744-6872
1744-6880
- Abstract
- 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 (Delta FEV1)] induced by 4 weeks of inhaled treatment with fluticasone propionate (1000 mu g 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 Delta FEV1. The Delta FEV1 of the -10073C/C homozygous genotype was twice that of the -10073G/G and -10073C/G genotypes (P-corr = 0.04 in recessive model). No splicing variant of WDR21A was observed, regardless of genotype. The predicted WDR21A protein structure was similar to the G beta(1) 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 G beta(1) proteins for binding to GRs. Pharmacogenetics and Genomics 22:327-335 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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