Association of season of birth with <scp>DNA</scp> methylation and allergic disease

Lockett, Gabrielle A.; Soto‐Ramírez, Nelís; Ray, Meredith; Everson, Todd M.; Xu, Cheng‐Jian; Patil, Veeresh; Terry, W. Robert; Kaushal, Akhilesh; Rezwan, Faisal I.; Ewart, Susan; Gehring, Ulrike; Postma, Dirkje S.; Koppelman, Gerard H.; Arshad, Syed Hasan; Zhang, H.; Karmaus, Wilfried; Holloway, John W.

doi:10.1111/all.12882

Cited by 68 publications

(59 citation statements)

References 47 publications

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“…Recently, one epigenome-wide association study was based on methylation measured in whole-blood DNA collected from 367 participants aged 18 years from the UK. The author reported that 92 CpG sites were associated with specific seasons of birth and 4 of these associations were replicated in an independent series of 207 children aged 8 years from The Netherlands [11]. The indirect effect of season of birth on AR at 6 years was found to be mediated by the level of methylation of the IFN-γ promoter methylation in our study.…”

Section: Discussionsupporting

confidence: 73%

“…The association of prenatal and early-life exposures and the subsequent development of allergy-related outcomes with focuses on different breastfeeding characteristics [5], mode of delivery [6], the microbiome [7], indoor allergens [8], and air pollution exposure [9] during the first months and years of life have been previously reported. In several studies, the season of birth has also been associated with the risk of developing allergic disease including rhinitis [10, 11] and hay fever [12]; however, the mechanisms underlying such effects remain unknown.…”

Section: Introductionmentioning

confidence: 99%

“…Epigenetic changes in DNA methylation are one way in which transcriptional responses to changing environments can be established and maintained over long periods of time. DNA methylation in adulthood is associated with the season of birth, suggesting that this association arises postnatally and could mediate the effect of season of birth on allergies [11]. The TH1/TH2 paradigm assumes that a predominance of TH2 cell activation and an inadequate TH1 cell response are responsible for the development of allergies.…”

Section: Introductionmentioning

confidence: 99%

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Early-Life Environmental Factors, IFN-γ Methylation Patterns, and Childhood Allergic Rhinitis

Rui

et al. 2019

Int Arch Allergy Immunol

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Background: While early-life risk factors are known to influence the risk of allergies, the biological mechanisms underlying this observation are unclear. The aim of this study was to examine whether DNA methylation in childhood could underlie the association between early-life risk factors and allergic rhinitis (AR). Methods: In total, 234 patients, aged 6 years, were recruited, i.e., 114 were patients with AR (AR group) and 120 healthy children without AR (NAR group). The DNA methylation patterns of the IFN-γ promoter regions in CD4+ cells were analyzed using bisulfite sequencing. The percentage of Th1 was investigated by flow cytometry. The relationship among DNA methylation, early-life environment, and AR was examined. Results: After adjusting for several likely confounders, there was a higher likelihood of AR in children who had mothers with allergies than in children who had nonallergic mothers (OR = 5.19; 95% CI 1.18–29.41), in children who were born in autumn or winter than in children who were born in the summer or spring (OR = 2.69; 95% CI 1.34–5.40), and in children who lived with indoor carpet or wallpaper than in children who lived without indoor carpet or wallpaper (OR = 4.14; 95% CI 2.05–8.30). Compared to the NAR group, the AR group had higher mean methylation levels of the promoter region in IFN-γY, and lower numbers of IFN-γ+CD4+ cells were associated with autumn-winter birthdates. The season of birth had an indirect effect on AR at 6 years, which was mediated by the mean IFN-γ promoter methylation level. Conclusions: This study suggests that early-life environments affect AR, and this is supported by the finding of IFN-γY methylation as a mediator of the effect of an individual’s season of birth on AR.

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Early-Life Environmental Factors, IFN-γ Methylation Patterns, and Childhood Allergic Rhinitis

Rui

et al. 2019

Int Arch Allergy Immunol

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“…χ 2 tests were used to test the independence of factors associated with breastfeeding duration (maternal socioeconomic status, maternal smoking during pregnancy, sibling order, season of birth, sex, parental history of allergy, RLRTI, birthweight, gestational age, and mode of delivery (9, 19–24)), to identify potential confounding factors. Where available these factors were also tested in the FAIR cohort to assess whether any associations have changed over time on the Isle of Wight.…”

Section: Methodsmentioning

confidence: 99%

Evaluating the efficacy of breastfeeding guidelines on long-term outcomes for allergic disease

Bion

Lockett

Soto‐Ramírez

et al. 2016

Allergy

Self Cite

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Background WHO guidelines advocate breastfeeding for six months, and EAACI recommends exclusive breastfeeding for 4–6 months. However, evidence for breastfeeding to prevent asthma and allergic disease is conflicting. We examined whether following recommended breastfeeding guidelines alters the long-term risks of asthma, eczema, rhinitis, or atopy. Methods The effect of non-exclusive (0, >0–6, >6 months), and exclusive breastfeeding (0, >0–4, >4 months) on repeated measures of asthma (10, 18 years), eczema, rhinitis, and atopy (1-or-2, 4, 10, 18 years) risks were estimated in the IoW cohort (n=1456) using log-linear models with generalised estimating equations. The Food Allergy and Intolerance Research (FAIR) cohort (n=988), also from the IoW, was examined to replicate results. Results Breastfeeding (any or exclusive) had no effect on asthma and allergic disease in the IoW cohort. In the FAIR cohort, any breastfeeding for >0–6 months protected against asthma at 10 years (RR=0.50, 95%CI=0.32–0.79, p=0.003) but not other outcomes, while exclusive breastfeeding for >4 months protected against repeated rhinitis (RR=0.36, 95%CI=0.18–0.71, p=0.003). Longer breastfeeding was protective against late-onset wheeze in the IoW cohort. Conclusion The protective effects of non-exclusive and exclusive breastfeeding against long-term allergic outcomes were inconsistent between these co-located cohorts, agreeing with previous observations of heterogeneous effects. Although breastfeeding should be recommended for other health benefits, following breastfeeding guidelines did not appear to afford consistent protection against long-term asthma, eczema, rhinitis or atopy. Further research is needed into the long-term effects of breastfeeding on allergic disease.

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“…Season-associated methylation was absent in newborns, suggesting it appears postnatal. 11 DNA methylation marks involved in T-cell maturation (RUNX3), type 2 immune response (IL4), and oxidative stress (catalase) were associated with allergic asthma in the inner city study. 12 In monozygotic twin pairs with discordance for asthma symptoms methylomic markers in peripheral blood differentiate remitting and persisting asthma.…”

mentioning

confidence: 97%

Endotypes of allergic diseases and asthma: An important step in building blocks for the future of precision medicine

Agache

Akdiş

2016

Allergology International

161

140

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Discoveries from basic science research in the last decade have brought significant progress in knowledge of pathophysiologic processes of allergic diseases, with a compelling impact on understanding of the natural history, risk prediction, treatment selection or mechanism-specific prevention strategies. The view of the pathophysiology of allergic diseases developed from a mechanistic approach, with a focus on symptoms and organ function, to the recognition of a complex network of immunological pathways. Several subtypes of inflammation and complex immune-regulatory networks and the reasons for their failure are now described, that open the way for the development of new diagnostic tools and innovative targeted-treatments. An endotype is a subtype of a disease condition, which is defined by a distinct pathophysiological mechanism, whereas a disease phenotype defines any observable characteristic of a disease without any implication of a mechanism. Another key word linked to disease endotyping is biomarker that is measured and evaluated to examine any biological or pathogenic processes, including response to a therapeutic intervention. These three keywords will be discussed more and more in the future with the upcoming efforts to revolutionize patient care in the direction of precision medicine and precision health. The understanding of disease endotypes based on pathophysiological principles and their validation across clinically meaningful outcomes in asthma, allergic rhinitis, chronic rhinosinusitis, atopic dermatitis and food allergy will be crucial for the success of precision medicine as a new approach to patient management.

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Association of season of birth with DNA methylation and allergic disease

Cited by 68 publications

References 47 publications

Early-Life Environmental Factors, IFN-γ Methylation Patterns, and Childhood Allergic Rhinitis

Early-Life Environmental Factors, IFN-γ Methylation Patterns, and Childhood Allergic Rhinitis

Evaluating the efficacy of breastfeeding guidelines on long-term outcomes for allergic disease

Endotypes of allergic diseases and asthma: An important step in building blocks for the future of precision medicine

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