Biochemical investigation of association of arsenic exposed polymorphic variants and disease susceptibility

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 vario...

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Main Authors: Syed Muhammad Shoaib, Samina Afzal, Muhammad Sajid Hamid Akash, Kanwal Rehman, Amjad Hussain, Ahmed Nadeem, Asif Shahzad, Sabry M. Attia
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-03-01
Series:Emerging Contaminants
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405665024000945
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author Syed Muhammad Shoaib
Samina Afzal
Muhammad Sajid Hamid Akash
Kanwal Rehman
Amjad Hussain
Ahmed Nadeem
Asif Shahzad
Sabry M. Attia
author_facet Syed Muhammad Shoaib
Samina Afzal
Muhammad Sajid Hamid Akash
Kanwal Rehman
Amjad Hussain
Ahmed Nadeem
Asif Shahzad
Sabry M. Attia
author_sort Syed Muhammad Shoaib
collection DOAJ
description 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.
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spelling doaj-art-15b2ca58ccff4e43b45eab6d1172c43f2025-08-20T03:10:30ZengKeAi Communications Co., Ltd.Emerging Contaminants2405-66502025-03-0111110039310.1016/j.emcon.2024.100393Biochemical investigation of association of arsenic exposed polymorphic variants and disease susceptibilitySyed Muhammad Shoaib0Samina Afzal1Muhammad Sajid Hamid Akash2Kanwal Rehman3Amjad Hussain4Ahmed Nadeem5Asif Shahzad6Sabry M. Attia7Department of Pharmaceutical Chemistry, Bahauddin Zakariya University, Multan, PakistanDepartment of Pharmaceutical Chemistry, Bahauddin Zakariya University, Multan, PakistanDepartment of Pharmaceutical Chemistry, Government College University, Faisalabad, Pakistan; Corresponding author.Department of Pharmacy, The Women University, Multan, PakistanInstitute of Chemistry, University of Okara, Okara, PakistanDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Biochemistry and Molecular Biology, Kunming Medical University, Yunnan, ChinaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaOur 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.http://www.sciencedirect.com/science/article/pii/S2405665024000945Metabolic disordersDimethylated arsenicMonomethylated arsenicArsenic methylationInflammatory biomarkersGSTT1 and GSTM1 polymorphisms
spellingShingle Syed Muhammad Shoaib
Samina Afzal
Muhammad Sajid Hamid Akash
Kanwal Rehman
Amjad Hussain
Ahmed Nadeem
Asif Shahzad
Sabry M. Attia
Biochemical investigation of association of arsenic exposed polymorphic variants and disease susceptibility
Emerging Contaminants
Metabolic disorders
Dimethylated arsenic
Monomethylated arsenic
Arsenic methylation
Inflammatory biomarkers
GSTT1 and GSTM1 polymorphisms
title Biochemical investigation of association of arsenic exposed polymorphic variants and disease susceptibility
title_full Biochemical investigation of association of arsenic exposed polymorphic variants and disease susceptibility
title_fullStr Biochemical investigation of association of arsenic exposed polymorphic variants and disease susceptibility
title_full_unstemmed Biochemical investigation of association of arsenic exposed polymorphic variants and disease susceptibility
title_short Biochemical investigation of association of arsenic exposed polymorphic variants and disease susceptibility
title_sort biochemical investigation of association of arsenic exposed polymorphic variants and disease susceptibility
topic Metabolic disorders
Dimethylated arsenic
Monomethylated arsenic
Arsenic methylation
Inflammatory biomarkers
GSTT1 and GSTM1 polymorphisms
url http://www.sciencedirect.com/science/article/pii/S2405665024000945
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