MicroRNAs play an important role in contributing to arsenic susceptibility in the chronically exposed individuals of West Bengal, India

Arsenic exposure by groundwater contamination is a menace which threatens more than 26 million individuals of West Bengal. Interestingly, with similar levels of arsenic exposure, only 15–20% of the population show arsenic-induced skin lesions, the hallmarks of chronic arsenic toxicity, but the rest do not. In this study, our aim was to identify whether microRNAs (miRNA) have any role to play in causing such arsenic susceptibility. Global plasma miRNA profiling was done in 12 arsenic-exposed individuals with skin lesions and 12 exposed individuals without skin lesions. Two hundred two miRNAs were found to be differentially regulated between the two study groups. Results were validated by quantitative real-time PCR in 30 exposed subjects from each of the groups, which showed that among others miR-21, miR-23a, miR-27a, miR-122, miR-124, miR-126, miR-619, and miR-3613 were significantly upregulated and miR-1282 and miR-4530 were downregulated in the skin lesion group compared with the no skin lesion group. Bioinformatic analyses predicted that these altered miRNAs have targets in 7 different biochemical pathways, including glycerophospholipid metabolism, colorectal cancer, glycosphingolipid biosynthesis, T cell receptor signaling, and neurotrophin signaling pathways; glycerophospholipid metabolism pathway being the most enriched pathway. Association study show that these microRNAs contribute significantly to the increased prevalence of other non-dermatological health effects like conjunctival irritations of the eyes and respiratory distress in the study subjects. To our knowledge, this is the first study of its kind involving miRNA expressions contributing to arsenic susceptibility in the exposed population of West Bengal.