Abstract
BackgroundChronic exposure to arsenic is associated with cancer and hypertension. Growing evidence suggests that altered methylation in long interspersed nuclear element-1 (LINE-1) is involved in many types of disorders, including cardiovascular disease. Here we evaluated the association between arsenic exposure and LINE-1 methylation levels, especially in relation to blood pressure (BP).MethodsA total of 236 subjects (175 from arsenic-endemic areas and 61 from a non-endemic area) in rural Bangladesh were recruited. The subjects’ arsenic exposure levels (i.e., drinking water, hair and nail arsenic concentrations) were measured by inductively coupled plasma mass spectroscopy. The subjects’ LINE-1 methylation levels were determined by pyrosequencing.ResultsThe average LINE-1 methylation levels of the subjects living in the arsenic-endemic areas were significantly (p < 0.01) lower than those of the subjects living in the non-endemic area. In a sex-stratified analysis, the arsenic exposure levels in female but not male subjects showed a significant inverse association with LINE-1 methylation levels before (water arsenic: p < 0.01, hair arsenic: p < 0.05, nail arsenic: p < 0.001) and after (water arsenic: p < 0.01, hair arsenic: p < 0.05, nail arsenic: p < 0.001) adjustment for age, body mass index and smoking. Analyses examining interactions among arsenic levels, BP and LINE-1 methylation showed that arsenic-related elevated levels of BP were associated with LINE-1 hypomethylation.ConclusionsOur findings demonstrated that chronic exposure to arsenic was inversely associated with LINE-1 methylation levels in blood leukocyte DNA and this was more pronounced in females than males; in addition, the decreased levels of LINE-1 methylation might be involved in the arsenic-induced elevation of BP.
Highlights
Chronic exposure to arsenic is associated with cancer and hypertension
In this study, we explored the association between arsenic exposure, as measured by drinking water, hair and nail arsenic concentrations, and long interspersed nuclear element-1 (LINE-1) methylation levels through a cross sectional study recruiting human subjects from arsenic-endemic and non-endemic areas in Bangladesh
No significant associations of arsenic exposure metrics with LINE-1 methylation levels were observed in the males, suggesting that the apparent associations between arsenic exposure and LINE-1 hypomethylation in all subjects may be a reflection of the significant association in females (Table 3)
Summary
Chronic exposure to arsenic is associated with cancer and hypertension. We evaluated the association between arsenic exposure and LINE-1 methylation levels, especially in relation to blood pressure (BP). Chronic exposure to arsenic is a major threat to the public health in many countries, including Bangladesh. Chronic exposure to arsenic has been associated with several neoplastic and nonneoplastic diseases [1,2,3]. Health outcomes of chronic exposure to arsenic are influenced by several genetic and non-genetic factors. The recent development of fine and robust epigenetic techniques and the growing evidence that supports the involvement of epigenetic modifications in cancer and Hossain et al Environmental Health (2017) 16:20 other diseases have created great interest in potential epigenetic biomarkers of arsenic-related diseases. Epigenetic changes, especially changes in DNA methylation have been reported to be implicated in the pathogenesis of many diseases [5,6,7,8,9]
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