title: Association between WDR21A polymorphisms and airway responsiveness to inhaled corticosteroids in asthmatic patients.
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 [FEV(1) (ΔFEV(1))] 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 ΔFEV(1). The ΔFEV(1) 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 Gβ(1) protein structure (template modeling-score=0.93).
  
  
  CONCLUSIONS
  The minor allele -10073C of WDR21A may induce a good response to inhaled corticosteroids possibly through competition with the Gβ(1) proteins for binding to GRs.
authors.affiliation: Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Wonmi-gu, Bucheon, Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Cho
authors.forename: Byung-Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Seung Woo
authors.initials: SW
authors.lastname: Shin
authors.forename: Jeong-Seok
authors.initials: JS
authors.lastname: Heo
authors.forename: Jong-Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
authors.forename: An-Soo
authors.initials: AS
authors.lastname: Jang
authors.forename: Il Yup
authors.initials: IY
authors.lastname: Chung
authors.forename: Houng-Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000235:genetics; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics; D054316:Biomarkers, Pharmacological; D002352:Carrier Proteins / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D054316:Biomarkers, Pharmacological; D002352:Carrier Proteins; C574006:DCAF4 protein, human; C501825:DCAF6 protein, human; D009687:Nuclear Proteins; D011965:Receptors, Glucocorticoid