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Amarasekera M.,University of Western Australia | Noakes P.,University of Western Australia | Strickland D.,Telethon Kids Institute | Saffery R.,Murdoch Childrens Research Institute | And 6 more authors.

Supplementation of fish oil rich in omega-3 polyunsaturated fatty acids (n-3 PUFA) during pregnancy has been shown to confer favorable health outcomes in the offspring. In a randomized controlled trial, we have previously shown that n-3 PUFA supplementation in pregnancy was associated with modified immune responses and some markers of immune maturation. However, the molecular mechanisms underlying these heritable effects are unclear. To determine whether the biological effects of maternal n-3 PUFA supplementation are mediated through DNA methylation, we analyzed CD4+ T-cells purified from cryo-banked cord blood samples from a previously conducted clinical trial. Of the 80 mother-infant pairs that completed the initial trial, cord blood samples of 70 neonates were available for genome-wide DNA methylation profiling. Comparison of purified total CD4+ T-cell DNA methylation profiles between the supplement and control groups did not reveal any statistically significant differences in CpG methylation, at the single-CpG or regional level. Effect sizes among top-ranked probes were lower than 5% and did not warrant further validation. Tests for association between methylation levels and key n-3 PUFA parameters, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), or total n-3 PUFAs were suggestive of dose-dependent effects, but these did not reach genome-wide significance. Our analysis of the microarray data did not suggest strong modifying effects of in utero n-3 PUFA exposure on CD4+ T-cell methylation profiles, and no probes on the array met our criteria for further validation. Other epigenetic mechanisms may be more relevant mediators of functional effects induced by n-3 PUFA in early life. © 2014 Taylor & Francis Group, LLC. Source

Amarasekera M.,University of Western Australia | Martino D.,Murdoch Childrens Research Institute | Martino D.,University of Melbourne | Martino D.,Center for Food and Allergy Research | And 8 more authors.
FASEB Journal

Folate intake during pregnancy may affect the regulation of DNA methylation during fetal development. The genomic regions in the offspring that may be sensitive to folate exposure during in utero development have not been characterized. Using genome-scale profiling, we investigated DNA methylation in 2 immune cell types (CD4+and antigen-presenting cells) isolated from neonatal cord blood, selected on the basis of in utero folate exposure. High-folate (HF; n=11) and low-folate (LF; n=12) groups were selected from opposite extremes of maternal serum folate levels measured in the last trimester of pregnancy. A comparison of these groups revealed differential methylation at 7 regions across the genome. By far, the biggest effect observed was hypomethylation of a 923 bp region 3 kb upstream of the ZFP57 transcript, a regulator of DNA methylation during development, observed in both cell types. Levels of H3/H4 acetylation at ZFP57 promoter and ZFP57 mRNA expression were higher in CD4+cells in the HF group relative to the LF group. Hypomethylation at this region was replicated in an independent sample set. These data suggest that exposure to folate has effects on the regulation of DNA methylation during fetal development, and this may be important for health and disease. © FASEB. Source

Ashley S.,Murdoch Childrens Research Institute | Ashley S.,Monash Institute of Medical Research | Dang T.,Murdoch Childrens Research Institute | Dang T.,Center for Food and Allergy Research | And 11 more authors.
Current Opinion in Allergy and Clinical Immunology

Purpose of review The community burden of food allergy appears to be rising, yet the causes and mechanisms are not completely understood. The purpose of this review is to provide a snapshot of the state of play of IgE food allergies, with a focus on recent advances. Recent findings There are still wide discrepancies regarding measures and definitions of food allergy. Even recent studies still rely on food sensitization, self-reporting, or parent-reporting rather than more robust measures. Population-based sampling strategies using objective measures are underway in some countries. Emerging data suggest substantial geographical and ethnic differences in food sensitization and allergy. Trans-cutaneous sensitization, particularly in those with eczema or filaggrin mutations, has been posited as a potential mechanism, as well as gut microbiota and genetics/epigenetics. Treatments for food allergy are still lacking, yet progress is being made, and immunotherapy appears more effective than dietary avoidance. Non-IgE food allergy remains drastically under-explored. Summary Food allergy is a complex immune-mediated disease consisting of numerous environmental/genetic/epigenetic risk factors; yet interventions are likely to be simple and cost-effective. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source

Molloy J.,Child Health Research Unit | Molloy J.,Deakin University | Molloy J.,Murdoch Childrens Research Institute | Molloy J.,Center for Food and Allergy Research | And 21 more authors.
Mini-Reviews in Medicinal Chemistry

Studies from several countries have reported an association between latitudes further from the equator and proxy markers of food allergy prevalence. As latitudes further from the equator are associated with lower sun exposure and vitamin D status (VDS), it has been proposed that low VDS may be a risk factor for food allergy. A range of basic science evidence supports the biological plausibility of this hypothesis; and recent work has identified a cross sectional association between low VDS and challenge proven food allergy in infants. Overall, however, the evidence regarding the relationship between VDS and food allergy remains controversial and the limited longitudinal data are discouraging. In this review we consider the evidence for and against low VDS as a risk factor for food allergy and discuss the possibility that other factors (including genetic variables) may contribute to the inconsistent nature of the available observational evidence. We then discuss whether genetic and/or environmental factors may modify the potential influence of VDS on food allergy risk. Finally, we argue that given the rising burden of food allergy, the balance of available evidence regarding the potential relevance of VDS to this phenomenon, and the inherent limitations of the existing observational data, there is a compelling case for conducting randomised clinical trials of vitamin D supplementation for the prevention of food allergy during early life. © 2015, Bentham Science Publishers. Source

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