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. 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

J A Curtin  1 , A Simpson, D Belgrave, A Semic-Jusufagic, A Custovic, F D Martinez
Affiliations

Methylation of IL-2 promoter at birth alters the risk of asthma exacerbations during childhood

J A Curtin et al. Clin Exp Allergy. 2013 Mar.

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 for asthma/wheeze between ages of 2 and 8 years.

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Conflict of interest statement

Conflict of interest: We declare that we have no conflict of interest in relation to this manuscript.

Figures

Fig. 1.
Fig. 1.
Conditional odds ratios for the change in the risk of hospital admission with asthma (a) and severe asthma exacerbation (b) with a unit increase in methylation level of IL-2 Site1.
Fig. 2.
Fig. 2.
IL-2 Site1 methylation and mononuclear cell lymphoproliferative response at birth.
See this image and copyright information in PMC

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