title: Epigenome-wide analysis of neonatal CD4(+) T-cell DNA methylation sites potentially affected by maternal fish oil supplementation.
abstract: 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.
authors.affiliation: a School of Pediatrics and Child Health ; University of Western Australia ; Perth , Australia.
authors.forename: Manori
authors.initials: M
authors.lastname: Amarasekera
authors.forename: Paul
authors.initials: P
authors.lastname: Noakes
authors.forename: Deborah
authors.initials: D
authors.lastname: Strickland
authors.forename: Richard
authors.initials: R
authors.lastname: Saffery
authors.forename: David J
authors.initials: DJ
authors.lastname: Martino
authors.forename: Susan L
authors.initials: SL
authors.lastname: Prescott
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000502:physiology*; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects*; D019587:Dietary Supplements; D044127:Epigenesis, Genetic; D004912:Erythrocytes / Q000187:drug effects; D005227:Fatty Acids / Q000097:blood*; D015525:Fatty Acids, Omega-3 / Q000097:blood / Q000494:pharmacology; D005260:Female; D005312:Fetal Blood / Q000187:drug effects; D005395:Fish Oils / Q000008:administration & dosage*; D055106:Genome-Wide Association Study; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy
chemical_list: D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D005395:Fish Oils
keywords: CBMC, cord blood mononuclear cells.; CD4+ T-cells; DHA; DHA, docosahexaenoic acid; DNA methylation; EPA; EPA, eicosapentaenoic acid; Fish oil; PUFA, polyunsaturated fatty acids; cord blood; maternal supplementation; n-3, omega 3; neonates; omega-3 fatty acids