Gene-Specific Differential DNA Methylation and Chronic Arsenic Exposure in an Epigenome-Wide Association Study of Adults in Bangladesh

被引:61
作者
Argos, Maria [1 ]
Chen, Lin [1 ]
Jasmine, Farzana [1 ]
Tong, Lin [1 ]
Pierce, Brandon L. [1 ]
Roy, Shantanu [1 ]
Paul-Brutus, Rachelle [1 ]
Gamble, Mary V. [2 ]
Harper, Kristin N. [2 ]
Parvez, Faruque [2 ]
Rahman, Mahfuzar [3 ]
Rakibuz-Zaman, Muhammad [3 ]
Slavkovich, Vesna [2 ]
Baron, John A. [4 ]
Graziano, Joseph H. [2 ]
Kibriya, Muhammad G. [1 ]
Ahsan, Habibul [1 ,5 ,6 ,7 ]
机构
[1] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA
[2] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA
[3] U Chicago Res Bangladesh, Dhaka, Bangladesh
[4] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA
[5] Univ Chicago, Dept Med, Chicago, IL 60637 USA
[6] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA
[7] Univ Chicago, Ctr Comprehens Canc, Chicago, IL 60637 USA
基金
美国国家卫生研究院;
关键词
PHOSPHOLIPASE A(2) ENZYMES; UMBILICAL-CORD BLOOD; INDUCED SKIN-LESIONS; UROTHELIAL CARCINOMAS; DRINKING-WATER; LEUKOCYTE DNA; KAPPA-B; CANCER; HYPERMETHYLATION; PROMOTER;
D O I
10.1289/ehp.1307884
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
BACKGROUND: Inorganic arsenic is one of the most common naturally occurring contaminants found in the environment. Arsenic is associated with a number of health outcomes, with epigenetic modification suggested as a potential mechanism of toxicity. Objective: Among a sample of 400 adult participants, we evaluated the association between arsenic exposure, as measured by blood and urinary total arsenic concentrations, and epigenome-wide white blood cell DNA methylation. METHODS: We used linear regression models to examine the associations between arsenic exposure and methylation at each CpG site, adjusted for sex, age, and batch. Differentially methylated loci were subsequently examined in relation to corresponding gene expression for functional evidence of gene regulation. RESULTS: In adjusted analyses, we observed four differentially methylated CpG sites with urinary total arsenic concentration and three differentially methylated CpG sites with blood arsenic concentration, based on the Bonferroni-corrected significance threshold of p < 1 x 10(-7). Methylation of PLA2G2C (probe cg04605617) was the most significantly associated locus in relation to both urinary (p = 3.40 x 10(-11)) and blood arsenic concentrations (p = 1.48 x 10(-11)). Three additional novel methylation loci-SQSTM1 (cg01225779), SLC4A4 (cg06121226), and IGH (cg13651690)-were also significantly associated with arsenic exposure. Further, there was evidence of methylation-related gene regulation based on gene expression for a subset of differentially methylated loci. CONCLUSIONS: We observed significant associations between arsenic exposure and gene-specific differential white blood cell DNA methylation, suggesting that epi-genetic modifications may be an important pathway under-lying arsenic toxicity. The specific differentially methylated loci identified may inform potential pathways for future interventions.
引用
收藏
页码:64 / 71
页数:8
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