Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing, China.
Toxicol Lett. 2011 May 30;203(1):48-53. doi: 10.1016/j.toxlet.2011.03.002. Epub 2011 Mar 9.
DNA methylation provides a plausible link between the environment and alterations in gene expression that may lead to disease phenotypes. Lead exposure can change DNA methylation status. Here, we hypothesized that the methylation of the ALAD gene promoter may play an important role in lead toxicity. To determine whether the methylation level of the ALAD promoter is associated with the risk of lead poisoning, we conducted a case-control study of 103 workers from a battery plant and 103 healthy volunteers with matching age and gender distribution. We employed real-time PCR and methylation-specific PCR (MSP) in cell models to determine the relationship between ALAD methylation level and transcription level. We found lead exposure to increase the ALAD gene methylation level and down-regulate ALAD transcription. The difference in methylation frequencies between exposures and controls was statistically significant (p=0.002), and individuals with methylated ALAD gene showed an increased risk of lead poisoning (adjusted OR=3.57, 95% CI, 1.55-8.18). This study suggests that the lead-exposure-induced increases in ALAD methylation may be involved in the mechanism of lead toxicity.
DNA 甲基化提供了一种环境与基因表达改变之间的可能联系，这种改变可能导致疾病表型。铅暴露可以改变 DNA 甲基化状态。在这里，我们假设 ALAD 基因启动子的甲基化可能在铅毒性中起重要作用。为了确定 ALAD 启动子的甲基化水平是否与铅中毒的风险相关，我们对来自电池厂的 103 名工人和 103 名年龄和性别匹配的健康志愿者进行了病例对照研究。我们在细胞模型中采用实时 PCR 和甲基化特异性 PCR（MSP）来确定 ALAD 甲基化水平与转录水平之间的关系。我们发现铅暴露会增加 ALAD 基因的甲基化水平并下调 ALAD 转录。暴露组和对照组之间的甲基化频率差异具有统计学意义（p=0.002），并且具有甲基化 ALAD 基因的个体患铅中毒的风险增加（调整后的 OR=3.57，95%CI，1.55-8.18）。这项研究表明，铅暴露诱导的 ALAD 甲基化增加可能参与了铅毒性的机制。
