Association Between Arsenic Metabolism Gene Polymorphisms and Arsenic-induced Skin Lesions in Individuals Exposed to High-dose Inorganic Arsenic in Northwest China

Overview

Journal Sci Rep

Specialty Science

Date 2018 Jan 12

PMID 29323258

Citations 8

Authors

Lanrong Luo

Yuanyuan Li

Yanhui Gao

Lijun Zhao

Hongqi Feng

Wei Wei

Chuanying Qiu

Qian He

Yanting Zhang

Songbo Fu

Dianjun Sun

Affiliations

Soon will be listed here.

Abstract

Individuals in a given environment contaminated with arsenic have different susceptibilities to disease, which may be related to arsenic metabolism, age, gender, genetics and other factors. This study recruited 850 subjects, including 331 cases and 519 controls, from populations exposed to high levels of arsenic in drinking water in northwest China. Genotypes were determined using a custom-by-design 48-Plex SNPscan kit. The results indicated that subjects who carried at least one C allele for GSTO1 rs11191979 polymorphism, at least one A allele for GSTO1 rs2164624, at least one A allele for GSTO1 rs4925, the AG genotype for GSTO2 rs156697, the AG genotype or at least one G allele for GSTO2 rs2297235 or the GG genotype or at least one G allele for PNP rs3790064 had an increased risk of arsenic-related skin lesions. In addition, the haplotype CT between rs4925 and rs11191979 appeared to confer a high risk of arsenic-included skin lesions (OR = 1.377, 95% CI = 1.03-1.84), as did the haplotype GCG among rs156697, rs157077 and rs2297235 (OR = 2.197, 95% CI = 1.08-4.44). The results showed that the variants of GSTO1, GSTO2 and PNP render the susceptible toward developing arsenic-induced skin lesions in individuals exposed to high-dose inorganic arsenic in northwest China.

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References

Nemeti B, Gregus Z . Glutathione-dependent reduction of arsenate in human erythrocytes--a process independent of purine nucleoside phosphorylase. Toxicol Sci. 2004; 82(2):419-28. DOI: 10.1093/toxsci/kfh301. View

Rodrigues E, Kile M, Hoffman E, Quamruzzaman Q, Rahman M, Mahiuddin G . GSTO and AS3MT genetic polymorphisms and differences in urinary arsenic concentrations among residents in Bangladesh. Biomarkers. 2012; 17(3):240-7. PMC: 3340466. DOI: 10.3109/1354750X.2012.658863. View

Xu Y, Wang J, Yin R, Qiu M, Xu L, Wang J . Genetic polymorphisms in Glutathione S-transferase Omega (GSTO) and cancer risk: a meta-analysis of 20 studies. Sci Rep. 2014; 4:6578. PMC: 4192632. DOI: 10.1038/srep06578. View

Rodriguez-Lado L, Sun G, Berg M, Zhang Q, Xue H, Zheng Q . Groundwater arsenic contamination throughout China. Science. 2013; 341(6148):866-8. DOI: 10.1126/science.1237484. View

Deng X, Yang X, Cheng Y, Liu X, Li X, Zhao R . GSTP1 and GSTO1 single nucleotide polymorphisms and the response of bladder cancer patients to intravesical chemotherapy. Sci Rep. 2015; 5:14000. PMC: 4564850. DOI: 10.1038/srep14000. View

Li Y, Martin E, Li Y . EMK: a novel program for family-based allelic and genotypic association tests on quantitative traits. Ann Hum Genet. 2008; 72(Pt 3):388-96. DOI: 10.1111/j.1469-1809.2008.00432.x. View

Hirakawa M, Tanaka T, Hashimoto Y, Kuroda M, Takagi T, Nakamura Y . JSNP: a database of common gene variations in the Japanese population. Nucleic Acids Res. 2001; 30(1):158-62. PMC: 99126. DOI: 10.1093/nar/30.1.158. View

Drobna Z, Waters S, Devesa V, Harmon A, Thomas D, Styblo M . Metabolism and toxicity of arsenic in human urothelial cells expressing rat arsenic (+3 oxidation state)-methyltransferase. Toxicol Appl Pharmacol. 2005; 207(2):147-59. PMC: 2366102. DOI: 10.1016/j.taap.2004.12.007. View

Hsu L, Wu M, Wang Y, Lee C, Yang T, Hsiao B . Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan. Biomed Res Int. 2015; 2015:892579. PMC: 4532812. DOI: 10.1155/2015/892579. View

10.

Paul S, Majumdar S, Giri A . Genetic susceptibility to arsenic-induced skin lesions and health effects: a review. Genes Environ. 2016; 37:23. PMC: 4917933. DOI: 10.1186/s41021-015-0023-7. View

11.

Gaxiola-Robles R, Labrada-Martagon V, Bitzer-Quintero O, Zenteno-Savin T, Mendez-Rodriguez L . Purine nucleoside phosphorylase and the enzymatic antioxidant defense system in breast milk from women with different levels of arsenic exposure. Nutr Hosp. 2015; 31(5):2289-96. DOI: 10.3305/nh.2015.31.5.8485. View

12.

Ahsan H, Chen Y, Kibriya M, Islam M, Slavkovich V, Graziano J . Susceptibility to arsenic-induced hyperkeratosis and oxidative stress genes myeloperoxidase and catalase. Cancer Lett. 2003; 201(1):57-65. DOI: 10.1016/s0304-3835(03)00471-3. View

13.

Whitbread A, Tetlow N, Eyre H, Sutherland G, Board P . Characterization of the human Omega class glutathione transferase genes and associated polymorphisms. Pharmacogenetics. 2003; 13(3):131-44. DOI: 10.1097/00008571-200303000-00003. View

14.

Schlawicke Engstrom K, Broberg K, Concha G, Nermell B, Warholm M, Vahter M . Genetic polymorphisms influencing arsenic metabolism: evidence from Argentina. Environ Health Perspect. 2007; 115(4):599-605. PMC: 1852682. DOI: 10.1289/ehp.9734. View

15.

De Chaudhuri S, Ghosh P, Sarma N, Majumdar P, Sau T, Basu S . Genetic variants associated with arsenic susceptibility: study of purine nucleoside phosphorylase, arsenic (+3) methyltransferase, and glutathione S-transferase omega genes. Environ Health Perspect. 2008; 116(4):501-5. PMC: 2291000. DOI: 10.1289/ehp.10581. View

16.

Gao J, Yu J, Yang L . Urinary arsenic metabolites of subjects exposed to elevated arsenic present in coal in Shaanxi Province, China. Int J Environ Res Public Health. 2011; 8(6):1991-2008. PMC: 3138009. DOI: 10.3390/ijerph8061991. View

17.

Jomova K, Jenisova Z, Feszterova M, Baros S, Liska J, Hudecova D . Arsenic: toxicity, oxidative stress and human disease. J Appl Toxicol. 2011; 31(2):95-107. DOI: 10.1002/jat.1649. View

18.

Djukic T, Simic T, Radic T, Matic M, Pljesa-Ercegovac M, Suvakov S . GSTO1*C/GSTO2*G haplotype is associated with risk of transitional cell carcinoma of urinary bladder. Int Urol Nephrol. 2015; 47(4):625-30. DOI: 10.1007/s11255-015-0933-0. View

19.

Josephy P . Genetic variations in human glutathione transferase enzymes: significance for pharmacology and toxicology. Hum Genomics Proteomics. 2010; 2010:876940. PMC: 2958679. DOI: 10.4061/2010/876940. View

20.

Hayes J, Flanagan J, Jowsey I . Glutathione transferases. Annu Rev Pharmacol Toxicol. 2005; 45:51-88. DOI: 10.1146/annurev.pharmtox.45.120403.095857. View