Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Epigenetics. 2013 May;8(5):494-503. doi: 10.4161/epi.24401. Epub 2013 May 1.
Dietary cadmium exposure was recently found to alter DNA methylation in adults, but data on effects early in life are lacking. Our objective was to evaluate associations between prenatal cadmium exposure, DNA methylation and birth weight. In total 127 mother-child pairs from rural Bangladesh were studied. For comparison, we included 56 children at 4.5 y. Cadmium concentrations in mothers' blood (gestational week 14) and children's urine were measured by ICPMS. Global DNA methylation was analyzed by Infinium HumanMethylation450K BeadChip in cord blood and children's blood. Maternal cadmium exposure was associated with cord blood DNA methylation (p-value < 10 (-16) ). The association was markedly sex-specific. In boys, 96% of the top 500 CpG sites showed positive correlations (rS-values > 0.50), whereas most associations in girls were inverse; only 29% were positive (rS > 0.45). In girls we found overrepresentation of methylation changes in genes associated with organ development, morphology and mineralization of bone, whereas changes in boys were found in cell death-related genes. Several individual CpG sites that were positively associated with cadmium were inversely correlated with birth weight, although none statistically significant after correction for multiple comparisons. The associations were, however, fairly robust in multivariable-adjusted linear regression models. We identified CpG sites that were significantly associated with cadmium exposure in both newborns and 4.5-y-old children. In conclusion, cadmium exposure in early life appears to alter DNA methylation differently in girls and boys. This is consistent with previous findings of sex-specific cadmium toxicity. Cadmium-related changes in methylation were also related to lower birth weight.
饮食中镉暴露最近被发现会改变成年人的 DNA 甲基化，但在生命早期的数据缺乏。我们的目的是评估产前镉暴露、DNA 甲基化与出生体重之间的关系。总共研究了来自孟加拉国农村的 127 对母婴。为了进行比较，我们还包括了 56 名 4.5 岁的儿童。通过 ICPMS 测量母亲血液（妊娠第 14 周）和儿童尿液中的镉浓度。通过 Infinium HumanMethylation450K BeadChip 在脐血和儿童血液中分析全基因组 DNA 甲基化。母体镉暴露与脐血 DNA 甲基化相关（p 值<10(-16)）。这种关联具有明显的性别特异性。在男孩中，前 500 个 CpG 位点中的 96%显示出正相关（rS 值>0.50），而女孩中的大多数关联则相反；只有 29%为正相关（rS >0.45）。在女孩中，我们发现与器官发育、骨骼形态和矿化相关的基因的甲基化变化占优势，而男孩中的变化则出现在与细胞死亡相关的基因中。有几个与镉呈正相关的个别 CpG 位点与出生体重呈负相关，尽管在进行多次比较校正后，没有一个具有统计学意义。然而，这些关联在多变量调整的线性回归模型中相当稳健。我们确定了在新生儿和 4.5 岁儿童中与镉暴露显著相关的 CpG 位点。总之，生命早期的镉暴露似乎会在男孩和女孩中以不同的方式改变 DNA 甲基化。这与先前关于镉毒性的性别特异性的发现一致。与镉相关的甲基化变化也与较低的出生体重有关。
