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首页> 外文期刊>Pharmacogenetics and genomics >Association between WDR21A polymorphisms and airway responsiveness to inhaled corticosteroids in asthmatic patients
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Association between WDR21A polymorphisms and airway responsiveness to inhaled corticosteroids in asthmatic patients

机译：WDR21A基因多态性与哮喘患者吸入皮质类固醇的气道反应性之间的关系

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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.
机译：目的：遗传多态性部分是导致中度至重度哮喘患者吸入皮质类固醇激素反应差异很大的原因。这项研究的目的是检查WDR21A中的多态性，该多态性编码一种假定的糖皮质激素受体（GR）相互作用蛋白，以了解其与皮质类固醇反应性的关系。方法：对230名哮喘患者进行了4周丙酸氟替卡松（每天1000μg）吸入治疗后，在1 s [FEV1（ΔFEV1）]引起的呼气量变化。使用TaqMan分析对WDR21A的15个单核苷酸多态性（SNP）进行基因分型，并使用11个SNP进行进一步分析。使用逆转录酶-PCR分析WDR21A转录本的变异剪接。使用基于模板的建模方法预测了WDR21A的蛋白质结构，并使用Zdock将其对接至GR。结果：在分析的11个SDR和3个单倍型的WDR21A中，只有内含子SNP -10073G> C似乎会影响ΔFEV1。 -10073C / C纯合基因型的ΔFEV1是-10073G / G和-10073C / G基因型的两倍（隐性模型中Pcorr = 0.04）。无论基因型如何，均未观察到WDR21A的剪接变体。预测的WDR21A蛋白结构与Gβ1蛋白结构相似（模板建模得分= 0.93）。结论：WDR21A的次要等位基因-10073C可能通过与Gβ1蛋白竞争结合GR而诱导对吸入皮质类固醇的良好反应。

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