Abstract
We carry out a study to analyze the relation between polymorphisms of GSTT1, GSTM1 and the capacity of arsenic methylation in a human population exposed to arsenic in drinking water. 230 randomly chose subjects were divided into four subgroups based on the arsenic levels, and then the associations between the polymorphisms of GSTT1, GSTM1 and methylation of arsenic were investigated. The levels of inorganic arsenic (iAs), monomethylated arsenic (MMA), dimethylated arsenic (DMA) and total arsenic (TAs) in urine were higher in males than that in females. Moreover, the levels of iAs and TAs in urine in the subjects with genotype of GSTM1(+) were significantly higher than those with GSTM1(−); the level of DMA in the subjects with GSTT1(+) and GSTM1(+) were higher than those with GSTT1(−) and GSTM1(−), although it is not statistically significant. Secondary methylation index (SMI) was significantly higher in the subjects with genotype of GSTT1(+) than those with GSTT1(−). The levels of TAs in urine, together with the genotypes of GSTT1/GSTM1 were associated with the levels of MMA and DMA. Our results suggested that the polymorphisms of GSTT1 and GSTM1 were associated with the methylation of arsenic, especially the levels of DMA and SMI.
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References
Smith, A.H., Lopipero, P.A., Bates, M.N. & Steinmaus, C.M. Public health. Arsenic epidemiology and drinking water standards. Science 296, 2145–2146 (2002).
Sun, X., Li, B., Li, X., Wang, Y., Xu, Y. & Jin, Y. et al. Effects of sodium arsenite on catalase activity, gene and protein expression in HaCaT cells. Toxicol. In Vitro 20, 1139–1144 (2006).
Chen, Y.C., Guo, Y.L., Su, H.J., Hsueh, Y.M., Smith, T.J. & Ryan, L.M. et al. Arsenic methylation and skin cancer risk in southwestern Taiwan. J. Occup. Environ. Med. 45, 241–248 (2003).
Chiou, H.Y., Hsueh, Y.M., Hsieh, L.L., Hsu, L.I., Hsu, Y.H. & Hsieh, F.I. et al 1997. Arsenic methylation capacity, body retention, and null genotypes of glutathione S-transferase M1 and T1 among current arsenic-exposed residents in Taiwan. Mutat. Res. 386, 197–207 (1997).
Vahter, M. Genetic polymorphism in the biotransformation of inorganic arsenic and its role in toxicity. Toxicol. Lett. 112-113, 209–217 (2000).
Luz Maria., D.R., Styblo, M., Cullen, W.R. & Thomas, D.J. Determination of trivalent methylated arsenicals in biological matrices. Toxicol. Appl. Pharmacol. 174, 282–293 (2001).
Kitchin, K.T. Recent advances in arsenic carcinogenesis: modes of action, animal model systems, and methylated arsenic metabolites. Toxicol. Appl. Pharmacol. 172, 249–261 (2001).
Styblo, M., Del Razo, L.M., Vega, L., Germolec, D.R., LeCluyse, E.L. & Hamilton, G.A. et al. Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells. Arch. Toxicol. 74, 289–299 (2000).
Sun, G., Xu, Y., Li, X., Jin, Y., Li, B. & Sun, X.. Urinary arsenic metabolites in children and adults exposed to arsenic in drinking water in Inner Mongolia, China. Environ. Health. Perspect. 115, 648–652 (2007).
Loffredo, C.A., Aposhian, H.V., Cebrian, M.E., Yamauchi, H. & Silbergeld, E.K. Variability in human metabolism of arsenic. Environ. Res. 92, 85–91 (2003).
McCarty, K.M., Chen, Y.C., Quamruzzaman, Q., Rahman, M., Mahiuddin, G. & Hsueh, Y.M. et al. Arsenic methylation, GSTT1, GSTM1, GSTP1 polymorphisms, and skin lesions. Environ. Health. Perspect. 115, 341–345 (2007).
McCarty, K.M., Ryan, L., Houseman, E.A., Williams, P.L., Miller, D.P. & Quamruzzaman, Q. et al. A case-control study of GST polymorphisms and arsenic related skin lesions. Environ. Health 6, 6:5 (2007).
Delnomdedieu, M., Basti, M.M., Otvos, J.D. & Thomas, D.J. Reduction and binding of arsenate and dimethylarsenate by glutathione: a magnetic resonance study. Chem. Biol. Interact. 90, 139–155 (1994).
Scott, N., Hatlelid, K.M., MacKenzie, N.E. & Carter, D.E. Reactions of arsenic (III) and arsenic (V) species with glutathione. Chem. Res. Toxicol. 6, 102–106 (1993).
Xu, C.M., Qian, Y.L. & Zhang, X. Correlation between genetic polymorphism in CYP2Z1, GST and toxicity of dimethylformamide. Zhong Guo Gong Ye Yi Xue Zazhi 20, 38–41 (2007).
Marcos, R., Martínez, V., Hernández, A., Creus, A., Sekaran, C. & Tokunaga, H. et al. Metabolic profile in workers occupationally exposed to arsenic: role of GST polymorphisms. J. Occup. Environ. Med. 48, 334–341 (2006).
Agusa, T., Iwata, H., Fujihara, J., Kunito, T., Takeshita, H. & Minh, T.B. et al. Genetic polymorphisms in glutathione S-transferase (GST) superfamily and arsenic metabolism in residents of the Red River Delta, Vietnam. Toxicol. Appl. Pharmacol. 242, 352–362 (2010).
Caceres, D.D., Werlinger, F., Orellana, M., Jara, M., Rocha, R. & Alvarado, S.A. et al. Polymorphism of glutathione S-transferase (GST) variants and its effect on distribution of urinary arsenic species in people exposed to low inorganic arsenic in tap water: an exploratory study. Arch. Environ. Occup. Health. 65, 140–147 (2010).
Su, L., Jin, Y., Cheng, Y. & Lin, S. Study on the relationship between GSTM1, GSTT1 gene polymorphisms and arsenic methylation level. Wei Sheng Yan Jiu 37, 432–434 (2008).
Rahbar, MH, Samms-Vaughan, M, Ma, J, Bressler, J, Loveland, KA & Ardjomand-Hessabi, M et al. Role of metabolic genes in blood arsenic concentrations of Jamaican children with and without autism spectrum disorder. Int. J. Environ. Res. Public Health 11, 7874–7895 (2014).
National Standard of P.R. China Standards for drinking water quality (2006) (GB 5749-2006) http://www.chinaios.com/.
World Health Organization Guidelines for drinking-water quality. 3rd 306 (WHO, Geneva, 2004).
Jin, Y.L. The paraphrase on standards for drinking water quality (GB5749-2006) 43–44 (China standard publishing house, Beijing, 2007).
Sun, D.J. To enhance the further field epidemiologic study on endemic arsenic poisoning in China. Zhong Guo Di Fang Bing Xue Zazhi 25, 1–2 (2006).
Zhang, M., Xiang, Q.Y. & Hu, X.S. Screening and spatial character of high arsenic-containing drinking water source in Jiangsu Province. Zhong Guo Gong Gong Wei Sheng 26, 170–171 (2010).
Chao, Y., Chen, J., Chao, J.W. & Qian, J.C. Application of Kish Grid sampling in world health Survey (China survey). Fudan Xue Bao (Yi Xue Ban) 31, 307–310 (2004).
Renata, N. (2002) Respondent Selection within the Household – A Modification of the Kish Grid http://www.math.uni-klu.ac.at/stat/Tagungen/Ossiach/Nemeth.pdf.
Xu, Y., Wang, Y., Zheng, Q., Li, B., Li, X.. & Jin, Y. et al. Clinical manifestations and arsenic methylation after a rare subacute arsenic poisoning accident. Toxicol. Sci. 103, 278–284 (2008).
Ren, W, Fan, Z, Guo, Y, Li, C & Bu, H Study on the genetic polymorphisms of human GSTT1 and GSTM1 in healthy population of Hebei Province. J. Brain Nervous Dis. 17, 88–92 (2009).
Sun, DJ. & Sun, G.F. Handbook of Endemic Arsenism Prevention and Control 7–11 (People’s medical publishing house Beijing, 2006).
Zhang, M., Xiang, Q.Y. & Hu, X.S. Analysis on the results of screening for the high level arsenic in drinking water in Jiangsu Province in 2005. Jiangsu Yu Fang Yi Xue 19, 1–4 (2008).
Li, X., Hou, P. & Sun, G. Effects of arsenic exposure through drinking water on methylation in persons. Wei Sheng Yan Jiu 37, 657–659 (2008).
Wang, H.X., Zheng, Q.M., Xi, S.H., Yang, J., Li, X. & Zhu, B. et al. Research on urinary arsenic metabolites of population exposed to different concentrations of arsenic by drinking water. Huan Jing Yu Jian Kang Za Zhi 26, 1041–1043 (2009).
Xu, Y.Y., Li, X., Liang, X.F., Jin, Y.P., Lu, C.W. & Li, G.X. et al. Study on urinary arsenic metabolites of population with different concentrations of arsenic in drinking water in Inner Mongolia. Zhong Guo Gong Gong Wei Sheng 22, 956–957 (2006).
Tseng, C.H., Huang, Y.K., Huang, Y.L., Chung, C.J., Yang, M.H. & Chen, C.J. et al. Arsenic exposure, urinary arsenic speciation, and peripheral vascular disease in blackfoot disease-hyperendemic villages in Taiwan. Toxicol. Appl. Pharmacol. 206, 299–308 (2005).
Sun, G.F. Advanced in pathogenesy research of arsenism caused by arsenic in drinking water. Yi Xue Yan Jiu Za Zhi 36, 2–4 (2007).
Chung, CJ, Huang, CY, Pu, YS, Shiue, HS, Su, CT & Hsueh, YM The effect of cigarette smoke and arsenic exposure on urothelial carcinoma risk is modified by glutathione S-transferase M1 gene null genotype. Toxicol. Appl. Pharmacol. 266, 254–259 (2013).
Keli, ML, Houseman, EA, Quamruzzaman, Q, Mahiuddin, G, Mostofa, G & Hsueh, YM Influence of GSTT1 genotic polymorphisms on arsenic metabolism. J. Indian Soc. Aqric. Stat. 67, 197–207 (2013).
Schläwicke-Engström, K, Broberg, K, Concha, G, Nermell, B, Warholm, M & Vahter, M. Genetic polymorphisms influencing arsenic metabolism: evidence from argentina. Environ. Health Perspect. 115, 599–605 (2007).
Andreae, M.O. Determination of arsenic species in natural waters. Anal. Chem. 49, 820–823 (1997).
Xu, Y.Y., He, M., Fu, J.P., Xue, P., Xu, L. & Sun, X.C. et al. Investigating arsenide speciation of drinking water in three endemic areas of China. Zhong Guo Di Fang Bing Xue Za Zhi 26, 173–175 (2007).
Zhu, B., Zheng, Q.M., Xu, Y.Y., Li, B. & Sun, G.F. Effects of smoking on arsenic metabolism, methylation: a meta-analysis. Huan Jing Yu Jian Kang Za Zhi 26, 1043–1045 (2009).
Acknowledgements
This work was supported by Jiangsu Province Association for Endemic Disease Control and Prevention (X200529) and the Natural Science Foundations of China (21277078). We thank Prof. Youxin Liang, (School of Public Health, Fudan Univesity), Liansheng Chen (Jiangsu Province Center for Diseases Control and Prevention) and Yewu Han (Xuyi County Center for Disease Control and Prevention) for their helps and valuable suggestions.
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Yang, J., Yan, L., Zhang, M. et al. Associations between the polymorphisms of GSTT1, GSTM1 and methylation of arsenic in the residents exposed to low-level arsenic in drinking water in China. J Hum Genet 60, 387–394 (2015). https://doi.org/10.1038/jhg.2015.39
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DOI: https://doi.org/10.1038/jhg.2015.39
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