Association of intronic polymorphisms (rs1549339, rs13402242) and mRNA expression variations in PSMD1 gene in arsenic-exposed workers.

Ubiquitin-proteasome system (UPS) gene, PSMD1, is an important gene for neutralization of damaged and misfolded protein(s). The current study was designed to study the genetic and expression variations of PSMD1 gene as a consequence of arsenic exposure and its potential implications in arsenic induced diseases. In the present study, 250 blood samples of exposed industrial workers along with 250 controls were used. Initially, tetra amplification refractory mutation system-PCR was used to determine the role of PSMD1 gene polymorphisms (rs1549339, rs13402242) in industrial workers and controls. Frequency of homozygous mutant genotype of rs1549339 (OR: 2.23, 95% CI: 1.51-3.32, p = 0.0001) and rs13402242 (OR: 2.96, 95% CI: 1.52-5.75, p = 0.001) was observed significantly higher in exposed individuals vs controls. Secondly, qPCR was performed for expression analysis of PSMD1 gene. Significant down-regulated expression of PSMD1 gene (p < 0.0001) was observed vs controls, and this down-regulation was observed more pronounced in smokers (p < 0.0001) with maximum exposure duration (p < 0.0008). This down-regulated expression was observed significantly more pronounced in welding (p < 0.004) and brick kiln industries (p < 0.04) compared to other selected industries. The obtained results suggest that the exposure to arsenic may have an increased risk of developing disease(s) because of arsenic-induced PSMD1 variations.