title: Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood.
abstract: Prenatal arsenic exposure is associated with increased risk of disease in adulthood. This has led to considerable interest in arsenic's ability to disrupt fetal programming. Many studies report that arsenic exposure alters DNA methylation in whole blood but these studies did not adjust for cell mixture. In this study, we examined the relationship between arsenic in maternal drinking water collected ≤ 16 weeks gestational age and DNA methylation in cord blood (n = 44) adjusting for leukocyte-tagged differentially methylated regions. DNA methylation was quantified using the Infinium HumanMethylation 450 BeadChip array. Recursively partitioned mixture modeling examined the relationship between arsenic and methylation at 473,844 CpG sites. Median arsenic concentration in water was 12 µg/L (range<1- 510 µg/L). Log 10 arsenic was associated with altered DNA methylation across the epigenome (P = 0.002); however, adjusting for leukocyte distributions attenuated this association (P = 0.013). We also observed that arsenic had a strong effect on the distribution of leukocytes in cord blood. In adjusted models, every log 10 increase in maternal drinking water arsenic exposure was estimated to increase CD8+ T cells by 7.4% (P = 0.0004) and decrease in CD4+ T cells by 9.2% (P = 0.0002). These results show that prenatal exposure to arsenic had an exposure-dependent effect on specific T cell subpopulations in cord blood and altered DNA methylation in cord blood. Future research is needed to determine if these small changes in DNA methylation alter gene expression or are associated with adverse health effects.
authors: Oregon State University; College of Public Health and Human Sciences; Corvallis, OR USA.
authors: Molly L
authors: ML
authors: Kile
authors: Oregon State University; College of Public Health and Human Sciences; Corvallis, OR USA.
authors: E Andres
authors: EA
authors: Houseman
authors: Harvard School of Public Health; Boston, MA USA.
authors: Andrea A
authors: AA
authors: Baccarelli
authors: Dhaka Community Hospital; Dhaka, Bangladesh.
authors: Quazi
authors: Q
authors: Quamruzzaman
authors: Dhaka Community Hospital; Dhaka, Bangladesh.
authors: Mahmuder
authors: M
authors: Rahman
authors: Dhaka Community Hospital; Dhaka, Bangladesh.
authors: Golam
authors: G
authors: Mostofa
authors: Oregon State University; College of Public Health and Human Sciences; Corvallis, OR USA.
authors: Andres
authors: A
authors: Cardenas
authors: Preventative Medicine and Pediatrics; Mt Sinai School of Medicine; New York, NY USA.
authors: Robert O
authors: RO
authors: Wright
authors: Harvard School of Public Health; Boston, MA USA.
authors: David C
authors: DC
authors: Christiani
mesh_terms: D001151:Arsenic / Q000633:toxicity*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D014874:Water Pollutants, Chemical; D001151:Arsenic
keywords: DNA methylation; arsenic; cord blood; developmental programming; immune function; leukocytes