Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes

Molly L. Kile, Andrea Baccarelli, Elaine Hoffman, Letizia Tarantini, Quazi Quamruzzaman, Mahmuder Rahman, Golam Mahiuddin, Golam Mostofa, Yu Mei Hsueh, Robert O. Wright, David C. Christiani

研究成果: 雜誌貢獻文章

92 引文 (Scopus)

摘要

Background: Arsenic is an epigenetic toxicant and could influence fetal developmental programming. Objectives: We evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes. Methods: Drinking-water and urine samples were collected when women were at ≤ 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was quantified using pyrosequencing in 113 pairs of maternal and umbilical blood samples. We used general linear models to evaluate the relationship between DNA methylation and tertiles of arsenic exposure. Results: Mean (± SD) drinking-water arsenic concentration was 14.8 ± 36.2 μg/L (range: <1-230 μg/L). Methylation in LINE-1 increased by 1.36% [95% confidence interval (CI): 0.52, 2.21%] and 1.08% (95% CI: 0.07, 2.10%) in umbilical cord and maternal leukocytes, respectively, in association with the highest versus lowest tertile of total urinary arsenic per gram creatinine. Arsenic exposure was also associated with higher methylation of some of the tested CpG sites in the promoter region of p16 in umbilical cord and maternal leukocytes. No associations were observed for Alu or p53 methylation. Conclusions: Exposure to higher levels of arsenic was positively associated with DNA methylation in LINE-1 repeated elements, and to a lesser degree at CpG sites within the promoter region of the tumor suppressor gene p16. Associations were observed in both maternal and fetal leukocytes. Future research is needed to confirm these results and determine if these small increases in methylation are associated with any health effects.

原文英語
頁(從 - 到)1061-1066
頁數6
期刊Environmental Health Perspectives
120
發行號7
DOIs
出版狀態已發佈 - 六月 2012

指紋

Arsenic
DNA Methylation
Fetal Blood
Leukocytes
Mothers
Methylation
Umbilical Cord
Genetic Promoter Regions
Drinking Water
Long Interspersed Nucleotide Elements
Alu Elements
Confidence Intervals
Umbilicus
Fetal Development
Tumor Suppressor Genes
Epigenomics
Linear Models
Mass Spectrometry
Creatinine
Urine

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health

引用此文

Kile, M. L., Baccarelli, A., Hoffman, E., Tarantini, L., Quamruzzaman, Q., Rahman, M., ... Christiani, D. C. (2012). Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes. Environmental Health Perspectives, 120(7), 1061-1066. https://doi.org/10.1289/ehp.1104173

Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes. / Kile, Molly L.; Baccarelli, Andrea; Hoffman, Elaine; Tarantini, Letizia; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Mostofa, Golam; Hsueh, Yu Mei; Wright, Robert O.; Christiani, David C.

於: Environmental Health Perspectives, 卷 120, 編號 7, 06.2012, p. 1061-1066.

研究成果: 雜誌貢獻文章

Kile, ML, Baccarelli, A, Hoffman, E, Tarantini, L, Quamruzzaman, Q, Rahman, M, Mahiuddin, G, Mostofa, G, Hsueh, YM, Wright, RO & Christiani, DC 2012, 'Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes', Environmental Health Perspectives, 卷 120, 編號 7, 頁 1061-1066. https://doi.org/10.1289/ehp.1104173
Kile ML, Baccarelli A, Hoffman E, Tarantini L, Quamruzzaman Q, Rahman M 等. Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes. Environmental Health Perspectives. 2012 6月;120(7):1061-1066. https://doi.org/10.1289/ehp.1104173
Kile, Molly L. ; Baccarelli, Andrea ; Hoffman, Elaine ; Tarantini, Letizia ; Quamruzzaman, Quazi ; Rahman, Mahmuder ; Mahiuddin, Golam ; Mostofa, Golam ; Hsueh, Yu Mei ; Wright, Robert O. ; Christiani, David C. / Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes. 於: Environmental Health Perspectives. 2012 ; 卷 120, 編號 7. 頁 1061-1066.
@article{ce6c3dcb9a62454c80795effbe66a257,
title = "Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes",
abstract = "Background: Arsenic is an epigenetic toxicant and could influence fetal developmental programming. Objectives: We evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes. Methods: Drinking-water and urine samples were collected when women were at ≤ 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was quantified using pyrosequencing in 113 pairs of maternal and umbilical blood samples. We used general linear models to evaluate the relationship between DNA methylation and tertiles of arsenic exposure. Results: Mean (± SD) drinking-water arsenic concentration was 14.8 ± 36.2 μg/L (range: <1-230 μg/L). Methylation in LINE-1 increased by 1.36{\%} [95{\%} confidence interval (CI): 0.52, 2.21{\%}] and 1.08{\%} (95{\%} CI: 0.07, 2.10{\%}) in umbilical cord and maternal leukocytes, respectively, in association with the highest versus lowest tertile of total urinary arsenic per gram creatinine. Arsenic exposure was also associated with higher methylation of some of the tested CpG sites in the promoter region of p16 in umbilical cord and maternal leukocytes. No associations were observed for Alu or p53 methylation. Conclusions: Exposure to higher levels of arsenic was positively associated with DNA methylation in LINE-1 repeated elements, and to a lesser degree at CpG sites within the promoter region of the tumor suppressor gene p16. Associations were observed in both maternal and fetal leukocytes. Future research is needed to confirm these results and determine if these small increases in methylation are associated with any health effects.",
keywords = "Alu, Arsenic, Developmental programming, DNA methylation, Environmental exposures, Epigenetics, In utero exposure, LINE-1, p16, p53",
author = "Kile, {Molly L.} and Andrea Baccarelli and Elaine Hoffman and Letizia Tarantini and Quazi Quamruzzaman and Mahmuder Rahman and Golam Mahiuddin and Golam Mostofa and Hsueh, {Yu Mei} and Wright, {Robert O.} and Christiani, {David C.}",
year = "2012",
month = "6",
doi = "10.1289/ehp.1104173",
language = "English",
volume = "120",
pages = "1061--1066",
journal = "Environmental Health Perspectives",
issn = "0091-6765",
publisher = "Public Health Services, US Dept of Health and Human Services",
number = "7",

}

TY - JOUR

T1 - Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes

AU - Kile, Molly L.

AU - Baccarelli, Andrea

AU - Hoffman, Elaine

AU - Tarantini, Letizia

AU - Quamruzzaman, Quazi

AU - Rahman, Mahmuder

AU - Mahiuddin, Golam

AU - Mostofa, Golam

AU - Hsueh, Yu Mei

AU - Wright, Robert O.

AU - Christiani, David C.

PY - 2012/6

Y1 - 2012/6

N2 - Background: Arsenic is an epigenetic toxicant and could influence fetal developmental programming. Objectives: We evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes. Methods: Drinking-water and urine samples were collected when women were at ≤ 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was quantified using pyrosequencing in 113 pairs of maternal and umbilical blood samples. We used general linear models to evaluate the relationship between DNA methylation and tertiles of arsenic exposure. Results: Mean (± SD) drinking-water arsenic concentration was 14.8 ± 36.2 μg/L (range: <1-230 μg/L). Methylation in LINE-1 increased by 1.36% [95% confidence interval (CI): 0.52, 2.21%] and 1.08% (95% CI: 0.07, 2.10%) in umbilical cord and maternal leukocytes, respectively, in association with the highest versus lowest tertile of total urinary arsenic per gram creatinine. Arsenic exposure was also associated with higher methylation of some of the tested CpG sites in the promoter region of p16 in umbilical cord and maternal leukocytes. No associations were observed for Alu or p53 methylation. Conclusions: Exposure to higher levels of arsenic was positively associated with DNA methylation in LINE-1 repeated elements, and to a lesser degree at CpG sites within the promoter region of the tumor suppressor gene p16. Associations were observed in both maternal and fetal leukocytes. Future research is needed to confirm these results and determine if these small increases in methylation are associated with any health effects.

AB - Background: Arsenic is an epigenetic toxicant and could influence fetal developmental programming. Objectives: We evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes. Methods: Drinking-water and urine samples were collected when women were at ≤ 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was quantified using pyrosequencing in 113 pairs of maternal and umbilical blood samples. We used general linear models to evaluate the relationship between DNA methylation and tertiles of arsenic exposure. Results: Mean (± SD) drinking-water arsenic concentration was 14.8 ± 36.2 μg/L (range: <1-230 μg/L). Methylation in LINE-1 increased by 1.36% [95% confidence interval (CI): 0.52, 2.21%] and 1.08% (95% CI: 0.07, 2.10%) in umbilical cord and maternal leukocytes, respectively, in association with the highest versus lowest tertile of total urinary arsenic per gram creatinine. Arsenic exposure was also associated with higher methylation of some of the tested CpG sites in the promoter region of p16 in umbilical cord and maternal leukocytes. No associations were observed for Alu or p53 methylation. Conclusions: Exposure to higher levels of arsenic was positively associated with DNA methylation in LINE-1 repeated elements, and to a lesser degree at CpG sites within the promoter region of the tumor suppressor gene p16. Associations were observed in both maternal and fetal leukocytes. Future research is needed to confirm these results and determine if these small increases in methylation are associated with any health effects.

KW - Alu

KW - Arsenic

KW - Developmental programming

KW - DNA methylation

KW - Environmental exposures

KW - Epigenetics

KW - In utero exposure

KW - LINE-1

KW - p16

KW - p53

UR - http://www.scopus.com/inward/record.url?scp=84863423870&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863423870&partnerID=8YFLogxK

U2 - 10.1289/ehp.1104173

DO - 10.1289/ehp.1104173

M3 - Article

C2 - 22466225

AN - SCOPUS:84863423870

VL - 120

SP - 1061

EP - 1066

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

SN - 0091-6765

IS - 7

ER -