Wheezing is a common and heterogeneous condition in preschool children. In some countries, the prevalence can be as high as 30% and up to 50% of all children experience wheezing before the age of 6. Asthma often starts with preschool wheeze, but not all wheezing children will develop asthma at school age. At this moment, it is not possible to accurately predict which wheezing children will develop asthma. Recently, studying the genetics of wheeze and the childhood-onset of asthma have grown in interest. Childhood-onset asthma has a stronger heritability in comparison with adult-onset asthma. In early childhood asthma exacerbations, CDHR3, which encodes the receptor for Rhinovirus C, was identified, as well as IL33, and the 17q locus that includes GSDMB and ORMDL3 genes. The 17q locus is the strongest wheeze and childhood-onset asthma locus, and was shown to interact with many environmental factors, including smoking and infections. Finally, ANXA1 was recently associated with early-onset, persistent wheeze. ANXA1 may help resolve eosinophilic inflammation. Overall, despite its complexities, genetic approaches to unravel the early-onset of wheeze and asthma are promising, since these shed more light on mechanisms of childhood asthma-onset. Implicated genes point toward airway epithelium and its response to external factors, such as viral infections. However, the heterogeneity of wheeze phenotypes complicates genetic studies. It is therefore important to define accurate wheezing phenotypes and forge larger international collaborations to gain a better understanding of the pathways underlying early-onset asthma.

中文翻译：

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学龄前喘息的遗传学及其进展为儿童哮喘

喘息是学龄前儿童的一种常见且异质性疾病。在一些国家，6 岁之前出现喘息的儿童患病率可能高达 30%，甚至高达 50%。哮喘通常始于学龄前喘息，但并非所有喘息儿童都会在学龄期患上哮喘。目前还无法准确预测哪些喘息儿童会患上哮喘。最近，人们对研究喘息遗传学和儿童期哮喘发病越来越感兴趣。与成人发病的哮喘相比，儿童期发病的哮喘具有更强的遗传性。在儿童早期哮喘急性发作中，编码鼻病毒 C 受体的CDHR3以及IL33和包含GSDMB和ORMDL3基因的 17q 基因座被鉴定出来。17q 位点是最强的喘息和儿童期哮喘位点，并被证明与许多环境因素相互作用，包括吸烟和感染。最后，ANXA1最近与早发型、持续性喘息相关。ANXA1可能有助于解决嗜酸性粒细胞炎症。总体而言，尽管其复杂性，揭示喘息和哮喘早期发作的遗传方法还是有希望的，因为这些方法可以更多地揭示儿童哮喘发作的机制。相关基因指向气道上皮及其对病毒感染等外部因素的反应。然而，喘息表型的异质性使遗传学研究变得复杂。因此，重要的是定义准确的喘息表型并建立更广泛的国际合作，以更好地了解早发性哮喘的潜在途径。