Klaassen Ester M M, Penders John, Jöbsis Quirijn, van de Kant Kim D G, Thijs Carel, Mommers Monique, van Schayck Constant P, van Eys Guillaume, Koppelman Gerard H, Dompeling Edward
Department of Paediatric Respiratory Medicine, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, the Netherlands.
Department of Epidemiology, CAPHRI, MUMC+, Maastricht, the Netherlands.
PLoS One. 2015 Mar 13;10(3):e0119349. doi: 10.1371/journal.pone.0119349. eCollection 2015.
The influence of asthma candidate genes on the development from wheeze to asthma in young children still needs to be defined.
To link genetic variants in asthma candidate genes to progression of wheeze to persistent wheeze into childhood asthma.
In a prospective study, children with recurrent wheeze from the ADEM (Asthma DEtection and Monitoring) study were followed until the age of six. At that age a classification (transient wheeze or asthma) was based on symptoms, lung function and medication use. In 198 children the relationship between this classification and 30 polymorphisms in 16 asthma candidate genes was assessed by logistic regression. In case of an association based on a p<0.10, replication analysis was performed in an independent birth cohort study (KOALA study, n = 248 included for the present analysis).
In the ADEM study, the minor alleles of ADAM33 rs511898 and rs528557 and the ORMDL3/GSDMB rs7216389 polymorphisms were negatively associated, whereas the minor alleles of IL4 rs2243250 and rs2070874 polymorphisms were positively associated with childhood asthma. When replicated in the KOALA study, ADAM33 rs528557 showed a negative association of the CG/GG-genotype with progression of recurrent wheeze into childhood asthma (0.50 (0.26-0.97) p = 0.04) and no association with preschool wheeze.
Polymorphisms in ADAM33, ORMDL3/GSDMB and IL4 were associated with childhood asthma in a group of children with recurrent wheeze. The replication of the negative association of the CG/GG-genotype of rs528557 ADAM33 with childhood asthma in an independent birth cohort study confirms that a compromised ADAM33 gene may be implicated in the progression of wheeze into childhood asthma.
哮喘候选基因对幼儿从喘息发展为哮喘的影响仍有待明确。
将哮喘候选基因中的遗传变异与喘息进展为持续性喘息并发展为儿童哮喘联系起来。
在一项前瞻性研究中，对来自ADEM（哮喘检测与监测）研究的复发性喘息儿童进行随访至6岁。在该年龄时，根据症状、肺功能和药物使用情况进行分类（短暂性喘息或哮喘）。对198名儿童，通过逻辑回归评估这种分类与16个哮喘候选基因中30个多态性之间的关系。若基于p<0.10存在关联，则在一项独立的出生队列研究（KOALA研究，本分析纳入248例）中进行重复分析。
在ADEM研究中，ADAM33基因的rs511898和rs528557的次要等位基因以及ORMDL3/GSDMB基因的rs7216389多态性与儿童哮喘呈负相关，而IL4基因的rs2243250和rs2070874多态性的次要等位基因与儿童哮喘呈正相关。在KOALA研究中进行重复分析时，ADAM33基因的rs528557的CG/GG基因型与复发性喘息发展为儿童哮喘呈负相关（0.50(0.26 - 0.97)，p = 0.04），与学龄前喘息无关联。
在一组复发性喘息儿童中，ADAM33、ORMDL3/GSDMB和IL4基因的多态性与儿童哮喘相关。在一项独立的出生队列研究中，rs528557 ADAM33的CG/GG基因型与儿童哮喘的负相关得到重复验证，证实ADAM33基因功能受损可能与喘息发展为儿童哮喘有关。
