University Clinical Centre Maribor, Maribor, Slovenia.
Int J Immunogenet. 2012 Feb;39(1):20-5. doi: 10.1111/j.1744-313X.2011.01051.x. Epub 2011 Oct 21.
Asthma is one of the most common chronic diseases in childhood. It is well known that genetic variability contributes to asthma risk. One of the most replicated asthma candidate genes is ORM1-like 3 (Saccharomyces cerevisiae) (ORMDL3), which has been associated with childhood asthma susceptibility. Another asthma candidate gene is signal transducer and activator of transcription 6 (STAT6), a regulator of IgE class switching. Gene coding thromboxane A2 receptor (TBXA2R), involved in chronic airway inflammation, has been associated with asthma in several genetic studies. We have studied the association of polymorphism rs4795405 in ORMDL3, rs324011 in STAT6 as well as rs8113232 and rs3786989 in TBXA2R with asthma risk, various asthma phenotypes and asthma-related symptoms. The study group consisted of 154 children with asthma, in whom clinical parameters were measured and whose asthma control and atopic status were determined. A control group comprised 71 healthy children. Genotyping was performed using an allelic discrimination assay. The ORMDL3 polymorphism rs4795405 was suggestively associated with asthma risk. Furthermore, it was significantly associated with nonatopic asthma and asthma without rhinitis. No association was detected between the STAT6 polymorphism rs324011 or the TBXA2R polymorphisms rs8113232 and rs3786989 and asthma susceptibility. However, an association between rs324011 in STAT6 with recurrent wheezing in early childhood and a suggestive association between rs8113232 in TBXA2R with rhinitis in children with asthma were observed. Our results confirmed ORMDL3 as a candidate gene for childhood asthma susceptibility. STAT6 and TBXA2R polymorphisms were not associated with asthma risk, but they were associated with asthma-related symptoms.
哮喘是儿童最常见的慢性疾病之一。众所周知，遗传变异性会导致哮喘风险。最具复制性的哮喘候选基因之一是ORM1 样 3（酿酒酵母）（ORMDL3），它与儿童哮喘易感性有关。另一个哮喘候选基因是信号转导和转录激活因子 6（STAT6），它是 IgE 类转换的调节剂。参与慢性气道炎症的血栓素 A2 受体（TBXA2R）基因编码，在几项遗传研究中与哮喘有关。我们研究了 ORMDL3 中的多态性 rs4795405、STAT6 中的 rs324011 以及 TBXA2R 中的 rs8113232 和 rs3786989 与哮喘风险、各种哮喘表型和哮喘相关症状的关联。研究组包括 154 名哮喘儿童，其中测量了临床参数，并确定了哮喘控制和特应性状态。对照组包括 71 名健康儿童。使用等位基因鉴别检测进行基因分型。ORMDL3 多态性 rs4795405 与哮喘风险呈显著关联。此外，它与非特应性哮喘和无鼻炎的哮喘显著相关。未检测到 STAT6 多态性 rs324011 或 TBXA2R 多态性 rs8113232 和 rs3786989 与哮喘易感性之间存在关联。然而，在 STAT6 中的 rs324011 与幼儿期反复喘息之间观察到关联，而在 TBXA2R 中的 rs8113232 与哮喘儿童的鼻炎之间观察到关联。我们的结果证实了 ORMDL3 是儿童哮喘易感性的候选基因。STAT6 和 TBXA2R 多态性与哮喘风险无关，但与哮喘相关症状有关。
