哮喘联盟

   摘要
   背景：表观遗传学修饰在哮喘易感性中发挥了作用。
   目的：本试验研究出生时对调节IL-2转录所必需的CpG位点（IL-2位点）进行表观遗传学修饰是否与儿童期哮喘发作有关。
   方法：评估303名儿童（225名为过敏性哮喘患儿）脐带血IL-2位点1的甲基化情况。对于对照者，检测与IL-2转录无关的位点的甲基化情况（IL-2位点7）和LINE-1重复原件的甲基化情况。受试者随访至8岁。根据儿童初级医疗机构中的病历记录，评价严重哮喘发作和住院治疗相关信息。为解释细支气管炎的潜在影响，我们采用1岁后哮喘发病/住院作为主要转归。
   结果：33名儿童中有49次严重哮喘发作，11名儿童中有22次住院治疗。IL-2位点1甲基化每增加1个百分点，哮喘发作增加1.07倍（95% CI 1.01-1.14, P=0.03），住院风险增加1.12倍（95% CI 1.04-1.20, P = 0.002）。任何时间点入院治疗的患儿，IL-1位点1甲基化水平高于无住院患儿（P=0.007）。哮喘发作（P=0.03）或住院（P=0.02）时的年龄与甲基化之间存在交互作用，且甲基化随着年龄的增加而增加。对照者IL-2位点7或LINE-1的甲基化不是哮喘发作/住院治疗的一个预测因子，而且IL-2位点1甲基化和其他原因导致的住院治疗之间无显著相关性（0.99 [0.92-1.06]）。脐带血单核细胞植物凝集素刺激的淋巴样增殖反应，随着IL-2位点1甲基化的增加显著下降（P<0.001）。
   结论：脐带血IL-2启动子功能性CpG位点甲基化增加与2～8岁时的严重哮喘发作和哮喘/喘息导致的住院治疗增加相关。          
 

(林江涛 审校)
Clin Exp Allergy. 2013 Mar;43(3):304-11. doi: 10.1111/cea.12046.

 

Methylation of IL-2 promoter at birth alters the risk of asthma exacerbations during childhood.
 
Curtin JA, Simpson A, Belgrave D, Semic-Jusufagic A, Custovic A, Martinez FD.

Source
The University of Manchester, Manchester Academic Health Science Centre, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.

Abstract 
BACKGROUND: Epigenetic modifications may have a role in asthma susceptibility.
OBJECTIVE: To investigate whether epigenetic modification at birth of a CpG site necessary for the regulation of IL-2 transcription (IL-2 Site1) is associated with the development of asthma during childhood.
METHODS: Methylation of IL-2 Site1 was assessed in cord blood from 303 children (225 with atopic mothers); as controls, we measured methylation of a site not important in the transcription of IL-2 (IL-2 Site7) and methylation of the LINE-1 repetitive element. Children were followed to the age of 8 years. Information on severe asthma exacerbations and hospital admissions was collected from child's primary care medical record. To account for potential confounding by bronchiolitis, we used exacerbations/hospitalizations after age 1 year as primary outcomes.
RESULTS: There were 49 severe exacerbations amongst 33 children, and 22 hospital admissions amongst 11 children. The risk of asthma exacerbation increased 1.07-fold (95% CI 1.01-1.14, P = 0.03) and the risk of hospital admission increased 1.12-fold (95% CI 1.04-1.20, P = 0.002) for each one per cent increase in IL-2 Site1 methylation. Children who were admitted to hospital at any time-point had significantly higher IL-2 Site1 methylation than children not admitted to hospital (P = 0.007). There was a significant interaction between age at exacerbation (P = 0.03) or hospital admission (P = 0.02) and methylation, with the effect of methylation increasing with increasing age. Methylation of the control IL-2 Site7 or LINE-1 was not a significant predictor of asthma exacerbations/hospital admission, and we found no association between IL-2 Site1 methylation and hospital admissions for other reasons (0.99 [0.92-1.06]). Cord blood mononuclear cell phytohemagglutinin-stimulated lymphoproliferative responses decreased significantly with increasing IL-2 Site1 methylation (P < 0.001).
CONCLUSIONS: Increasing methylation in cord blood of a functional CpG site in the IL-2 promoter is associated with increased likelihood of severe asthma exacerbations and hospital admissions forasthma/wheeze between ages of 2 and 8 years.

Clin Exp Allergy. 2013 Mar;43(3):304-11. doi: 10.1111/cea.12046.