Genomic DNA hydroxymethylation reveals potential role in identification of lung injury in coal-burning arsenicosis populations

Arsenic (As) is a toxic metalloid element that causes lung cancer and multiple non-malignant respiratory diseases. The toxicity of arsenic is mediated in part by epigenetic mechanisms, such as alterations in DNA methylation. While increasing studies have highlighted the potential importance of arsenic exposure to DNA methylation patterns and the subsequent risks for arsenic toxicity, there has been little focus on DNA hydroxymethylation-a negative regulation mechanism of DNA methylation. Therefore, this study aimed to investigate the relationship between genomic DNA methylation/hydroxymethylation and lung injury in arsenicosis populations. First, an increased risk of lung injury and exacerbation of lung function impairment in the arsenicosis population was confirmed. Levels of 5-methylcytosine/deoxycytidine (5 mC/dC), 5-hydroxymethylcytosine/ deoxycytidine (5 hmC/dC) and 5 hmC/5 mC in genomic DNA of peripheral blood were decreased in the arsenicosis population compared to in the control. Additionally, multivariate logistic regression models showed an increased risk of chest digital radiography (DR) abnormalities when 5 hmC/dC and 5 hmC/5 mC levels were lower (OR = 3.12 and 3.96, all P < 0.001). For 3 years follow-up, regression analysis showed that a decline in 5 hmC/dC was significantly associated with the decline of lung function parameters [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and maximal mid-expiratory flow (MMEF); beta = 0.167, 0.122 and 0.073, respectively; all P < 0.05]. Using the receiver operating characteristic (ROC) curve, a combination of 5 hmC/5 dC and 5 hmC/5 mC obtained the highest value for distinguishing lung injury in all subjects (AUC = 0.82, P < 0.01). In contrast, in arsenicosis subjects, 5 hmC/dC was better at distinguishing lung injury (AUC = 0.84, P < 0.01). Together, the results revealed that a decrease in genomic DNA hydroxymethylation markers was associated with lung injury in coal-burning arsenicosis populations. Genomic DNA hydroxymethylation could be a novel biomarker for identifying the risk of lung injury caused by coal-burning arsenicosis.

Automated summary

The study confirmed increased risk of lung injury and exacerbation of lung function impairment in arsenicosis populations. Decreased levels of genomic DNA methylation and hydroxymethylation were associated with these lung injuries. Genomic DNA hydroxymethylation could be a novel biomarker for identifying the risk of lung injury in coal-burning arsenicosis populations.