哮喘联盟

   摘要
   基因变异可以部分解释哮喘治疗反应存在差异。我们的研究目的是对于那些采用了吸入性糖皮质激素治疗（ICS）但仍没能很好控制的哮喘患者，了解这类哮喘相关的常见或罕见的基因变异。儿童哮喘治疗优化试验收集了110例儿童的数据。 通过使用外显子组芯片，分析基因变异与肺功能(FEV1%预计值), 乙酰甲胆碱(Mch PD20)测定的 气道高反应性 (AHR) 和治疗反应结果三者的相关性。17q12-21 基因座 (含有ORMDL3和 GSMDB) 之前被认为与儿童哮喘相关而个别被研究。17q12-21 基因座的单核苷酸多态性 (SNPs) 名义上被发现与结果有关。这个区域最强的相关性是 KRT25 的rs72821893与FEV1%预计值 (P=3.75*10-5)，与Mch PD20 (P=0.00095) 、与基于Mch PD20的治疗结果 (P=0.006)。没有新的SNPs位点或负荷实验与治疗效果显著相关。17q12-21 区域与FEV1%预计值和AHR，以及与吸入性糖皮质激素治疗反应均具有相关性。
 

（杨冬 审校）
Pharmacogenomics J. 2015 May 12. doi: 10.1038/tpj.2015.36. [Epub ahead of print]

 

Genetic variation in uncontrolled childhood asthma despite ICS treatment.
 

Leusink M1, Vijverberg SJ2, Koenderman L3, Raaijmakers JA4, de Jongste JC5, Sterk PJ6, Duiverman EJ7, Onland-Moret NC8, Postma DS9, de Boer A4, de Bakker PI10, Koppelman GH7, Maitland-van der Zee AH4.
Author information
 

Abstract
Genetic variation may partly explain asthma treatment response heterogeneity. We aimed to identify common and rare genetic variants associated with asthma that was not well controlled despite inhaled corticosteroid (ICS) treatment. Data of 110 children was collected in the Children Asthma Therapy Optimal trial. Associations of genetic variation with measures of lung function (FEV1%pred), airway hyperresponsiveness (AHR) to methacholine (Mch PD20) and treatment response outcomes were analyzed using the exome chip. The 17q12-21 locus (containing ORMDL3 and GSMDB) previously associated with childhood asthma was investigated separately. Single-nucleotide polymorphisms (SNPs) in the 17q12-21 locus were found nominally associated with the outcomes. The strongest association in this region was found for rs72821893 in KRT25 with FEV1%pred (P=3.75*10-5), Mch PD20 (P=0.00095) and Mch PD20-based treatment outcome (P=0.006). No novel single SNPs or burden tests were significantly associated with the outcomes. The 17q12-21 region was associated with FEV1%pred and AHR, and additionally with ICS treatment response.The Pharmacogenomics Journal advance online publication, 12 May 2015; doi:10.1038/tpj.2015.36.

Pharmacogenomics J. 2015 May 12. doi: 10.1038/tpj.2015.36. [Epub ahead of print]