Association between WDR21A polymorphisms and airway responsiveness to inhaled corticosteroids in asthmatic patients.
Pharmacogenet Genomics
; 22(5): 327-35, 2012 May.
Article
em En
| MEDLINE
| ID: mdl-22366774
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 Gß(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 Gß(1) proteins for binding to GRs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
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Corticosteroides
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Biomarcadores Farmacológicos
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Estudos de Associação Genética
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article