Cardenas Andres, Houseman E Andres, Baccarelli Andrea A, Quamruzzaman Quazi, Rahman Mahmuder, Mostofa Golam, Wright Robert O, Christiani David C, Kile Molly L
a School of Biological and Population Health Sciences; College of Public Health and Human Sciences; Oregon State University ; Corvallis , OR USA.
b Harvard T.H. Chan School of Public Health ; Boston , MA USA.
Epigenetics. 2015;10(11):1054-63. doi: 10.1080/15592294.2015.1105424.
Exposure to arsenic early in life has been associated with increased risk of several chronic diseases and is believed to alter epigenetic programming in utero. In the present study, we evaluate the epigenome-wide association of arsenic exposure in utero and DNA methylation in placenta (n = 37), umbilical artery (n = 45) and human umbilical vein endothelial cells (HUVEC) (n = 52) in a birth cohort using the Infinium HumanMethylation450 BeadChip array. Unadjusted and cell mixture adjusted associations for each tissue were examined along with enrichment analyses relative to CpG island location and omnibus permutation tests of association among biological pathways. One CpG in artery (cg26587014) and 4 CpGs in placenta (cg12825509; cg20554753; cg23439277; cg21055948) reached a Bonferroni adjusted level of significance. Several CpGs were differentially methylated in artery and placenta when controlling the false discovery rate (q-value<0.05), but none in HUVEC. Enrichment of hypomethylated CpG islands was observed for artery while hypermethylation of open sea regions were present in placenta relative to prenatal arsenic exposure. The melanogenesis pathway was differentially methylated in artery (Max F P < 0.001), placenta (Max F P < 0.001), and HUVEC (Max F P = 0.02). Similarly, the insulin-signaling pathway was differentially methylated in artery (Max F P = 0.02), placenta (Max F P = 0.02), and HUVEC (Max F P = 0.02). Our results show that prenatal arsenic exposure can alter DNA methylation in artery and placenta but not in HUVEC. Further studies are needed to determine if these alterations in DNA methylation mediate the effect of prenatal arsenic exposure and health outcomes later in life.
生命早期接触砷与多种慢性疾病风险增加有关，并且被认为会改变子宫内的表观遗传编程。在本研究中，我们使用Infinium HumanMethylation450 BeadChip芯片阵列，评估了一个出生队列中子宫内砷暴露与胎盘（n = 37）、脐动脉（n = 45）和人脐静脉内皮细胞（HUVEC）（n = 52）中DNA甲基化的全表观基因组关联。检查了每个组织的未调整和细胞混合物调整后的关联，以及相对于CpG岛位置的富集分析和生物途径间关联的综合置换检验。动脉中的一个CpG（cg26587014）和胎盘中的4个CpG（cg12825509；cg20554753；cg23439277；cg21055948）达到了Bonferroni校正的显著水平。在控制错误发现率（q值<0.05）时，动脉和胎盘中有几个CpG存在差异甲基化，但在HUVEC中没有。相对于产前砷暴露，观察到动脉中低甲基化CpG岛的富集，而胎盘中存在开放海域区域的高甲基化。黑色素生成途径在动脉（最大F P < 0.001）、胎盘（最大F P < 0.001）和HUVEC（最大F P = 0.02）中存在差异甲基化。同样，胰岛素信号通路在动脉（最大F P = 0.02）、胎盘（最大F P = 0.02）和HUVEC（最大F P = 0.02）中存在差异甲基化。我们的结果表明，产前砷暴露可改变动脉和胎盘中的DNA甲基化，但不会改变HUVEC中的DNA甲基化。需要进一步研究来确定这些DNA甲基化改变是否介导产前砷暴露的影响以及生命后期的健康结果。
