Abstract

Our study aimed to establish the association of polymorphic variants and disease susceptibility in arsenic-induced metabolic disorders raised due to the variability of arsenic methylation in human population exposed to arsenic in drinking water. Water samples were systematically collected from various regions of Faisalabad, Pakistan, and subjected to arsenic quantification through inductively coupled plasma emission spectrophotometry (ICP-OES). The groundwater exhibited significantly elevated arsenic concentrations (68.18 ± 21.28 μg/L) in comparison to both water and sanitation agency Faisalabad (WASA)-supplied water (9.81 ± 1.2 μg/L) and locally filtered water (8.12 ± 1.42 μg/L), as determined by one-way ANOVA followed by Bonferroni's post-test at P < 0.05. An association was established between arsenic concentration and the incidence of disease, such as diabetes mellitus. A cohort of 120 participants residing in six areas of District Faisalabad was recruited. Urine and blood specimens were collected for analysis. Urine samples underwent ICP-MS analysis in helium collision mode, utilizing germanium as an internal standard. Blood samples were collected for biomarker assessments, including HbA1c, BUN, creatinine, CRP, ALT, AST, GSH, SOD, and MDA, to investigate the evidence of diabetes mellitus. Urinary arsenic concentrations were found to be considerably higher (P < 0.05) in about 22.50 % of the participants, with a mean value of 68.43 ± 16.73 ppb. Biomarker analysis in these participants revealed mean values for BUN (37.19 ± 2.87 mg/dL), creatinine (2.58 ± 0.18 mg/dL), IL-6 (11.35 ± 6.98 pg/mL), CRP (1.90 ± 0.26 mg/dL), MDA (3.70 ± 0.18 nmol/mL), ALT (40.27 ± 5.41 U/L), and AST (38.92 ± 4.72 U/L). Furthermore, the gender-based analysis indicated the higher levels of DMA, MMA, TAs, and TiAs in males compared to females when urine samples were analyzed with HPLC-ICP-MS. Participants with the positive genotype of GSTM exhibited significantly higher levels of TAs, and TiAs concentration in their urine than those with the null genotype of GSTM. Moreover, participants with positive genotypes for GSTT1 and GSTM1 demonstrated elevated levels of DMA in their urine compared to those with genotypes of GSTT1 (−) and GSTM1 (−), although this difference did not attain statistical significance. Participants with the genotype of GSTT1 (+) displayed a considerably higher secondary methylation index than those with genotype of GSTT1 (−). MMA and DMA levels were found to be correlated with the genotypes of GSTT1 and GSTM1 and the amounts of TAs in urine. In conclusion, our findings suggest a linkage between arsenic methylation, particularly levels of DMA and SMI, and GSTT1 and GSTM1 polymorphisms.