General Hospital Dr Josip Bencevic Slavonski Brod, University of Osijek, Osijek, Croatia.
Ann Allergy Asthma Immunol. 2013 May;110(5):347-353.e2. doi: 10.1016/j.anai.2013.01.021. Epub 2013 Mar 6.
17q12-21 polymorphisms are associated with asthma presence and severity across different populations.
To extensively investigate the genes in this region among Croatian schoolchildren in a case-control study, taking account of early-life environmental exposures.
We included 423 children with asthma and 414 controls aged 5 to 18 years. Fifty-one haplotype tagging single-nucleotide polymorphisms (SNPs) were genotyped (GSDMA, GSDMB, ORMDL3, IKZF3, ZPBP2, and TOP2). Data on exposure to smoking and furry pet ownership were collected using a validated questionnaire. Information on severe asthma exacerbations with hospital admission were retrieved from hospital notes. All patients underwent spirometry.
We found 2 SNPs (1 novel rs9635726 in IKZF3) to be associated with asthma. Among children with asthma, 4 SNPs (in ZPBP2, GSDMB, and GSDMA) were associated with hospital admissions and 8 SNPs with lung function. One SNP (rs9635726) remained significantly associated with a predicted forced expiratory volume in 1 second after false discovery rate correction. Nine markers across 5 genes showed interaction with early-life environmental tobacco smoke (ETS) exposure in relation to asthma and 2 with furry pet ownership. Among children with asthma, we observed significant interactions between early-life ETS exposure and 3 SNPs for lung function and among early-life ETS exposure, 3 SNPs (in ORMDL3 and GSDMA), and hospital admission with asthma exacerbation. Three SNPs (in ORMDL3) interacted with current furry pet ownership in relation to hospital admissions for asthma exacerbation.
Our results indicate that several genes in the 17q12-21 region may be associated with asthma. This study confirms that environmental exposures may need to be included into the genetic association studies.
17q12-21 多态性与不同人群的哮喘存在和严重程度有关。
在一项病例对照研究中，广泛研究克罗地亚学龄儿童该区域的基因，并考虑到生命早期的环境暴露。
我们纳入了 423 名哮喘儿童和 414 名年龄在 5 至 18 岁的对照。对 51 个单核苷酸多态性（SNP）进行基因分型（GSDMA、GSDMB、ORMDL3、IKZF3、ZPBP2 和 TOP2）。使用经过验证的问卷收集有关吸烟和养宠物的暴露数据。从医院记录中检索因严重哮喘发作而住院的信息。所有患者均进行了肺活量测定。
我们发现 2 个 SNP（IKZF3 中的 1 个新 SNP rs9635726）与哮喘有关。在哮喘儿童中，4 个 SNP（ZPBP2、GSDMB 和 GSDMA）与住院有关，8 个 SNP 与肺功能有关。在经过假发现率校正后，1 个 SNP（rs9635726）仍与预测的 1 秒用力呼气量显著相关。跨越 5 个基因的 9 个标记物在与生命早期环境烟草烟雾（ETS）暴露相关的哮喘方面表现出相互作用，2 个标记物在与养宠物相关的哮喘方面表现出相互作用。在哮喘儿童中，我们观察到生命早期 ETS 暴露与 3 个 SNP 之间的显著相互作用，与肺功能有关，而生命早期 ETS 暴露与 3 个 SNP（ORMDL3 和 GSDMA）之间的相互作用，以及哮喘加重与住院之间的相互作用。3 个 SNP（ORMDL3）与当前养宠物之间的相互作用与哮喘加重的住院有关。
我们的研究结果表明，17q12-21 区域的几个基因可能与哮喘有关。本研究证实，环境暴露可能需要纳入遗传关联研究。
