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背景 17q21区域遗传变异及由病毒诱导的呼吸道喘息性疾病均与哮喘发病相关。此研究目的为将儿童期哮喘起因研究(COAST)及哥本哈根儿童期哮喘出生群体前瞻性研究(COPSAC)中的这两种因素对哮喘风险的作用进行检验。方法研究者检测了与哮喘、人类鼻病毒(HRV)及呼吸道合胞病毒(RSV)喘息性疾病相关的17q21区域基因型,也检测了17q21基因型与HRV和RSV喘息性疾病之间的交互作用所致的哮喘风险。最后,研究者检测了未加刺激及HRV刺激外周血液单核细胞(PBMCs)17q21特定基因型的表达。结果 17q21变异体与幼儿HRV喘息性疾病相关,但与RSV喘息性疾病无关。17q21变异与哮喘的关联仅限于曾患过HRV喘息性疾病的儿童,导致了与哮喘风险相关的明显的交互作用。此外,与未刺激PBMCs比较,HRV刺激PBMCs导致ORMDL3和GSDMB的表达水平升高。在以上条件中这些基因表达与17q21变异相关,HRV暴露的增加并不是特定基因的作用。结论 17q21区域的基因变异与曾患过HRV喘鸣性疾病儿童哮喘及此区域两种基因表达相关。两种基因的表达水平随着HRV刺激反应应答而增强,这种相关增强与17q21基因型无关。
Background 17q21 regional genetic variation and viral-induced respiratory asthmatic diseases are associated with asthma. The aim of this study was to examine the role of these two factors in asthma risk in the COAST (Childhood Asthma Initiation Study) and Prospective Cohorts in the Childhood Asthma Outcome in Copenhagen (COPSAC). METHODS: The investigators examined the 17q21 region genotypes associated with asthmatic, human rhinovirus (HRV) and respiratory syncytial virus (RSV) wheezing and also examined the interaction between the 17q21 genotype and HRV and RSV wheezy disease Caused by asthma risk. Finally, the researchers examined the expression of 17q21-specific genotypes in peripheral blood mononuclear cells (PBMCs) stimulated with and without stimulation of HRV. Results The 17q21 variant was associated with asthmatic HRV infants but not RSV wheezy. The association of the 17q21 mutation with asthma is restricted to children who have had HRV wheezy disease, resulting in a significant interaction with asthma risk. In addition, stimulation of PBMCs by HRV resulted in increased expression of ORMDL3 and GSDMB compared to non-stimulated PBMCs. In these conditions, the expression of these genes is correlated with the 17q21 mutation, and the increase in HRV exposure is not specific gene-specific. Conclusion The genetic variation in 17q21 region is associated with asthma in children with wheezing HRV and expression of two genes in this region. The level of expression of both genes increased with response to HRV stimulation response, and this increase was unrelated to the 17q21 genotype.