title: Associations between post translational histone modifications, myelomeningocele risk, environmental arsenic exposure, and folate deficiency among participants in a case control study in Bangladesh.
abstract: Arsenic exposure may contribute to disease risk in humans through alterations in the epigenome. Previous studies reported that arsenic exposure is associated with changes in plasma histone concentrations. Posttranslational histone modifications have been found to differ between the brain tissue of human embryos with neural tube defects and that of controls. Our objectives were to investigate the relationships between plasma histone 3 levels, history of having an infant with myelomeningocele, biomarkers of arsenic exposure, and maternal folate deficiency. These studies took place in Bangladesh, a country with high environmental arsenic exposure through contaminated drinking water. We performed ELISA assays to investigate plasma concentration of total histone 3 (H3) and the histone modification H3K27me3. The plasma samples were collected from 85 adult women as part of a case-control study of arsenic and myelomeningocele risk in Bangladesh. We found significant associations between plasma %H3K27me3 levels and risk of myelomeningocele (P<0.05). Mothers with higher %H3K27me3 in their plasma had lower risk of having an infant with myelomeningocele (odds ratio: 0.91, 95% confidence interval: 0.84, 0.98). We also found that arsenic exposure, as estimated by arsenic concentration in toenails, was associated with lower total H3 concentrations in plasma, but only among women with folate deficiency (β = -9.99, standard error = 3.91, P=0.02). Our results suggest that %H3K27me3 in maternal plasma differs between mothers of infants with myelomeningocele and mothers of infants without myelomeningocele, and may be a marker for myelomeningocele risk. Women with folate deficiency may be more susceptible to the epigenetic effects of environmental arsenic exposure.
authors.affiliation: a Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: Jannah
authors.initials: J
authors.lastname: Tauheed
authors.affiliation: a Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.|b Department of Developmental Neurobiology , National Institute of Perinatology , Mexico City , Mexico.
authors.forename: Marco
authors.initials: M
authors.lastname: Sanchez-Guerra
authors.affiliation: a Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.|c Department of Neurology , Boston Children's Hospital , Boston , MA , USA.
authors.forename: Jane J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: d Jean Mayer USDA Human Nutrition Research Center on Aging , Tufts University , Boston , MA , USA.
authors.forename: Ligi
authors.initials: L
authors.lastname: Paul
authors.affiliation: e Dhaka Community Hospital , Dhaka , Bangladesh.
authors.forename: Md Omar Sharif
authors.initials: MOS
authors.lastname: Ibne Hasan
authors.affiliation: e Dhaka Community Hospital , Dhaka , Bangladesh.
authors.forename: Quazi
authors.initials: Q
authors.lastname: Quamruzzaman
authors.affiliation: d Jean Mayer USDA Human Nutrition Research Center on Aging , Tufts University , Boston , MA , USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Selhub
authors.affiliation: f Department of Preventive Medicine , Icahn School of Medicine at Mount Sinai , New York , NY , USA.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Wright
authors.affiliation: a Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: David C
authors.identifier: 0000-0002-0301-0242
authors.initials: DC
authors.lastname: Christiani
authors.affiliation: g Department of Biostatistics , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Coull
authors.affiliation: h Department of Environmental Health Sciences , Columbia Mailman School of Public Health , New York , NY , USA.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
authors.affiliation: a Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.|c Department of Neurology , Boston Children's Hospital , Boston , MA , USA.
authors.forename: Maitreyi
authors.initials: M
authors.lastname: Mazumdar
mesh_terms: D000328:Adult; D001151:Arsenic / Q000633:toxicity; D001459:Bangladesh; D016022:Case-Control Studies; D060766:Drinking Water / Q000009:adverse effects; D004781:Environmental Exposure; D057890:Epigenomics; D005260:Female; D005494:Folic Acid Deficiency / Q000097:blood* / Q000139:chemically induced / Q000235:genetics; D042421:Histone Code; D006657:Histones / Q000097:blood*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D008591:Meningomyelocele / Q000097:blood* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D011247:Pregnancy; D011499:Protein Processing, Post-Translational / Q000235:genetics; D012307:Risk Factors; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: D060766:Drinking Water; D006657:Histones; D014874:Water Pollutants, Chemical; D001151:Arsenic
keywords: Arsenic; epigenetics; folate deficiency; histone modification; myelomeningocele