한국환경보건학회지 (Journal of Environmental Health Sciences)

  • 제47권6호
  • /
  • Pages.530-539
  • /
  • 2021
  • /
  • 1738-4087(pISSN)
  • /
  • 2233-8616(eISSN)
한국환경보건학회 (Korean Society of Environmental Health)
권호 표지
DOI QR코드

DOI QR Code

폐금속광산 지역 주민의 비소 대사에 영향을 미치는 MTHFR, As3MT, GSTO1 유전자 다형성

MTHFR, As3MT and GSTO1 Polymorphisms Influencing Arsenic Metabolism in Residents Near Abandoned Metal Mines in South Korea

  • 울지 (동아대학교 의과대학 예방의학교실) ;
  • 김병권 (동아대학교 의과대학 예방의학교실) ;
  • 손현진 (동아대학교 의과대학 예방의학교실) ;
  • 조성식 (동아대학교 의과대학 직업환경의학교실) ;
  • 김권민 (동아대학교 중금속노출 환경보건센터) ;
  • 임현주 (동아대학교 중금속노출 환경보건센터) ;
  • 권정연 (동아대학교 의과대학 예방의학교실) ;
  • 김기환 ((주)젠큐브플러스) ;
  • 홍영습 (동아대학교 의과대학 예방의학교실)
  • Surenbaatar, Ulziikhishig (Department of Preventive Medicine, College of Medicine, Dong-A University) ;
  • Kim, Byoung-Gwon (Department of Preventive Medicine, College of Medicine, Dong-A University) ;
  • Son, Hyun-Jin (Department of Preventive Medicine, College of Medicine, Dong-A University) ;
  • Cho, Seong-Sik (Department of Occupational and Environmental Medicine, College of Medicine, Dong-A University) ;
  • Kim, Gwon-Min (Heavy Metal Exposure Environmental Health Center, Dong-A University) ;
  • Lim, Hyoun-Ju (Heavy Metal Exposure Environmental Health Center, Dong-A University) ;
  • Kwon, Jung-Yeon (Department of Preventive Medicine, College of Medicine, Dong-A University) ;
  • Kim, Ki-Hwan (GENCUBEPLUS Co., Ltd) ;
  • Hong, Young-Seoub (Department of Preventive Medicine, College of Medicine, Dong-A University)
  • 투고 : 2021.09.28
  • 심사 : 2021.11.25
  • 발행 : 2021.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Background: In South Korea, areas around abandoned metal mines are designated as regions with high arsenic (As) contamination. However, studies assessing urinary As exposure, As metabolism, and relevant genetic polymorphisms in residents of these metal mine areas are lacking. Objectives: To identify factors associated with As exposure and evaluate the effects of MTHFR, As3MT, and GSTO1 genetic polymorphisms on As metabolism in residents of abandoned metal mine areas by measuring urinary As species. Methods: Urinary As species (arsenite [As3+], arsenate [As5+], monomethyl arsonic acid, and dimethylarsinic acid) were isolated using high-performance liquid chromatography in combination with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). Four genetic polymorphisms (MTHFR A222V, MTHFR E429A, GSTO1 A140D, As3MT M287T) were analyzed in 144 residents of four areas around abandoned metal mines. Results: The study sample was comprised of 34.7% men and 65.3% women, with a mean age of 70.7±10.9 years. The urinary inorganic As concentration was higher among those consuming more than half locally produced rice (0.31 ㎍/L) than those consuming less than half such rice (0.18 ㎍/L). The urinary dimethylarsinic acid concentration was higher in the group that had consumed seafood in the past day (31.68 ㎍/L) than in those who had not (22.37 ㎍/L). Furthermore, individuals heterozygous in the MTHFR A222V and GSTO1 A140D polymorphism had higher urinary arsenic species concentrations than did individuals with a wild type or homozygous for the variant allele. Conclusions: Consumption of locally produced rice was associated with inorganic As exposure, whereas seafood consumption was associated with organic As exposure among residents of abandoned metal mine areas. There was no clear association between MTHFR A222V and GSTO1 A140D polymorphisms and As metabolism.

키워드

과제정보

본 연구는 환경부 지정 동아대학교 중금속노출 환경보건센터의 지원을 받아 수행되었으며 이에 감사드립니다(IRB No. 2-1040709-AB-N-01-201908-BR-012-04).

참고문헌

  1. Mandal BK, Suzuki KT. Arsenic round the world: a review. Talanta. 2002; 58(1): 201-235. https://doi.org/10.1016/S0039-9140(02)00268-0
  2. Ministry of Food and Drug Safety/National Institute of Food and Drug Safety Evaluation. Exposure Assessment to Arsenic by Total Arsenic and Speciation Analyses in Urine. Cheongju: Ministry of Food and Drug Safety; 2014.
  3. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Arsenic. 2007. Available: https://www.atsdr.cdc.gov/toxprofiledocs/index.html [accessed 25 April 2021].
  4. Hong YS, Ye BJ, Kim YM, Kim BG, Kang GH, Kim JJ, et al. Investigation of health effects according to the exposure of low concentration arsenic contaminated ground water. Int J Environ Res Public Health. 2017; 14(12): 1461. https://doi.org/10.3390/ijerph14121461
  5. Seo JW, Choi JW, Oh YJ, Hong YS. Biological monitoring of arsenic concentrations according to exposure to arsenic-contaminated ground water. J Environ Health Sci. 2020; 46(5): 513-524. https://doi.org/10.5668/JEHS.2020.46.5.513
  6. Bae HS, Ryu DY, Choi BS, Park JD. Urinary arsenic concentrations and their associated factors in Korean adults. Toxicol Res. 2013; 29(2): 137-142. https://doi.org/10.5487/TR.2013.29.2.137
  7. Vahter M. Mechanisms of arsenic biotransformation. Toxicology. 2002; 181-182: 211-217. https://doi.org/10.1016/S0300-483X(02)00285-8
  8. Tseng CH. Arsenic methylation, urinary arsenic metabolites and human diseases: current perspective. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2007; 25(1): 1-22. https://doi.org/10.1080/10590500701201695
  9. Vahter M. Variation in human metabolism of arsenic. In: Chappell WR, Abernathy CO, Calderon RL. editors. Arsenic Exposure and Health Effects III, 1st ed. Oxford: Elsevier Science; 1999. p.267-279.
  10. Hughes MF, Beck BD, Chen Y, Lewis AS, Thomas DJ. Arsenic exposure and toxicology: a historical perspective. Toxicol Sci. 2011; 123(2): 305-332. https://doi.org/10.1093/toxsci/kfr184
  11. Petrick JS, Ayala-Fierro F, Cullen WR, Carter DE, Vasken Aposhian H. Monomethylarsonous acid (MMA(III)) is more toxic than arsenite in Chang human hepatocytes. Toxicol Appl Pharmacol. 2000; 163(2): 203-207. https://doi.org/10.1006/taap.1999.8872
  12. Styblo M, Drobna Z, Jaspers I, Lin S, Thomas DJ. The role of biomethylation in toxicity and carcinogenicity of arsenic: a research update. Environ Health Perspect. 2002; 110(Suppl 5): 767-771.
  13. Engstrom K, Vahter M, Mlakar SJ, Concha G, Nermell B, Raqib R, et al. Polymorphisms in arsenic(+III oxidation state) methyltransferase (AS3MT) predict gene expression of AS3MT as well as arsenic metabolism. Environ Health Perspect. 2011; 119(2): 182-188. https://doi.org/10.1289/ehp.1002471
  14. Lindberg AL, Kumar R, Goessler W, Thirumaran R, Gurzau E, Koppova K, et al. Metabolism of low-dose inorganic arsenic in a central European population: influence of sex and genetic polymorphisms. Environ Health Perspect. 2007; 115(7): 1081-1086. https://doi.org/10.1289/ehp.10026
  15. McClintock TR, Chen Y, Bundschuh J, Oliver JT, Navoni J, Olmos V, et al. Arsenic exposure in Latin America: biomarkers, risk assessments and related health effects. Sci Total Environ. 2012; 429: 76-91. https://doi.org/10.1016/j.scitotenv.2011.08.051
  16. Chung JY, Lim HJ, Kim YJ, Song KH, Kim BG, Hong YS. The separation of arsenic metabolites in urine by high performance liquid chromatographyinductively coupled plasma-mass spectrometry. Environ Health Toxicol. 2014; 29: e2014018. https://doi.org/10.5620/eht.e2014018
  17. Bustaffa E, Gorini F, Bianchi F, Minichilli F. Factors affecting arsenic methylation in contaminated Italian areas. Int J Environ Res Public Health. 2020; 17(14): 5226. https://doi.org/10.3390/ijerph17145226
  18. Tseng CH. A review on environmental factors regulating arsenic methylation in humans. Toxicol Appl Pharmacol. 2009; 235(3): 338-350. https://doi.org/10.1016/j.taap.2008.12.016
  19. Surenbaatar U, Seo JW, Kim BG, Lim HJ, Chang JY, Lee CW. Urinary arsenic species concentrations and related factors among residents living near abandoned metal mines. J Environ Health Sci. 2020; 46(6): 655-666. https://doi.org/10.5668/JEHS.2020.46.6.655
  20. 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. 2007; 115(4): 648-652. https://doi.org/10.1289/ehp.9271
  21. Del Razo LM, Garcia-Vargas GG, Vargas H, Albores A, Gonsebatt ME, Montero R, et al. Altered profile of urinary arsenic metabolites in adults with chronic arsenicism. A pilot study. Arch Toxicol. 1997; 71(4): 211-217. https://doi.org/10.1007/s002040050378
  22. Gomez-Rubio P, Roberge J, Arendell L, Harris RB, O'Rourke MK, Chen Z, et al. Association between body mass index and arsenic methylation efficiency in adult women from southwest U.S. and northwest Mexico. Toxicol Appl Pharmacol. 2011; 252(2): 176-182. https://doi.org/10.1016/j.taap.2011.02.007
  23. Chang JY, Ahn SC, Lee JS, Kim JY, Jung AR, Park J, et al. Exposure assessment for the abandoned metal mine area contaminated by arsenic. Environ Geochem Health. 2019; 41(6): 2443-2458. https://doi.org/10.1007/s10653-019-00296-5
  24. Cho Y, Seo S, Choi SH, Lee S, Kim K, Kim HJ, et al. Association of arsenic levels in soil and water with urinary arsenic concentration of residents in the vicinity of closed metal mines. Int J Hyg Environ Health. 2013; 216(3): 255-262. https://doi.org/10.1016/j.ijheh.2012.05.003
  25. Chung JY, Kim BG, Lee BK, Moon JD, Sakong J, Jeon MJ, et al. Urinary arsenic species concentration in residents living near abandoned metal mines in South Korea. Ann Occup Environ Med. 2016; 28: 67. https://doi.org/10.1186/s40557-016-0150-z
  26. Fu S, Wu J, Li Y, Liu Y, Gao Y, Yao F, et al. Urinary arsenic metabolism in a Western Chinese population exposed to high-dose inorganic arsenic in drinking water: influence of ethnicity and genetic polymorphisms. Toxicol Appl Pharmacol. 2014; 274(1): 117-123. https://doi.org/10.1016/j.taap.2013.11.004
  27. Schlawicke Engstrom K, Nermell B, Concha G, Stromberg U, Vahter M, Broberg K. Arsenic metabolism is influenced by polymorphisms in genes involved in one-carbon metabolism and reduction reactions. Mutat Res. 2009; 667(1-2): 4-14. https://doi.org/10.1016/j.mrfmmm.2008.07.003
  28. Huang YK, Tseng CH, Huang YL, Yang MH, Chen CJ, Hsueh YM. Arsenic methylation capability and hypertension risk in subjects living in arseniasis-hyperendemic areas in southwestern Taiwan. Toxicol Appl Pharmacol. 2007; 218(2): 135-142. https://doi.org/10.1016/j.taap.2006.10.022
  29. Li X, Li B, Xu Y, Wang Y, Jin Y, Itoh T, et al. Arsenic methylation capacity and its correlation with skin lesions induced by contaminated drinking water consumption in residents of chronic arsenicosis area. Environ Toxicol. 2011; 26(2): 118-123. https://doi.org/10.1002/tox.20535
  30. Melak D, Ferreccio C, Kalman D, Parra R, Acevedo J, Perez L, et al. Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile. Toxicol Appl Pharmacol. 2014; 274(2): 225-231. https://doi.org/10.1016/j.taap.2013.11.014
  31. Fujihara J, Soejima M, Koda Y, Kunito T, Takeshita H. Asian specific low mutation frequencies of the M287T polymorphism in the human arsenic (+3 oxidation state) methyltransferase (AS3MT) gene. Mutat Res. 2008; 654(2): 158-161. https://doi.org/10.1016/j.mrgentox.2008.06.001
  32. Gonzalez-Martinez F, Sanchez-Rodas D, Varela NM, Sandoval CA, Quinones LA, Johnson-Restrepo B. As3MT and GST polymorphisms influencing arsenic metabolism in human exposure to drinking groundwater. Int J Mol Sci. 2020; 21(14): 4832. https://doi.org/10.3390/ijms21144832
  33. Steinmaus C, Moore LE, Shipp M, Kalman D, Rey OA, Biggs ML, et al. Genetic polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and metabolism of arsenic. J Toxicol Environ Health A. 2007; 70(2): 159-170. https://doi.org/10.1080/15287390600755240
  34. De Chaudhuri S, Ghosh P, Sarma N, Majumdar P, Sau TJ, Basu S, et al. 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): 501-505. https://doi.org/10.1289/ehp.10581
  35. Luo L, Li Y, Gao Y, Zhao L, Feng H, Wei W, et al. Association between arsenic metabolism gene polymorphisms and arsenic-induced skin lesions in individuals exposed to high-dose inorganic arsenic in northwest China. Sci Rep. 2018; 8(1): 413. https://doi.org/10.1038/s41598-017-18925-3
  36. Chen JW, Wang SL, Wang YH, Sun CW, Huang YL, Chen CJ, et al. Arsenic methylation, GSTO1 polymorphisms, and metabolic syndrome in an arseniasis endemic area of southwestern Taiwan. Chemosphere. 2012; 88(4): 432-438. https://doi.org/10.1016/j.chemosphere.2012.02.059
  37. Paiva L, Marcos R, Creus A, Coggan M, Oakley AJ, Board PG. Polymorphism of glutathione transferase Omega 1 in a population exposed to a high environmental arsenic burden. Pharmacogenet Genomics. 2008; 18(1): 1-10. https://doi.org/10.1097/FPC.0b013e3282f29663
  38. Board PG, Coggan M, Chelvanayagam G, Easteal S, Jermiin LS, Schulte GK, et al. Identification, characterization, and crystal structure of the Omega class glutathione transferases. J Biol Chem. 2000; 275(32): 24798-24806. https://doi.org/10.1074/jbc.M001706200
  39. Xu Y, Li X, Zheng Q, Wang H, Wang Y, Sun G. Lack of association of glutathione-S-transferase omega 1(A140D) and omega 2 (N142D) gene polymorphisms with urinary arsenic profile and oxidative stress status in arsenic-exposed population. Mutat Res. 2009; 679(1-2): 44-49. https://doi.org/10.1016/j.mrgentox.2009.07.008
  40. Chung CJ, Pu YS, Su CT, Huang CY, Hsueh YM. Gene polymorphisms of glutathione S-transferase omega 1 and 2, urinary arsenic methylation profile and urothelial carcinoma. Sci Total Environ. 2011; 409(3): 465-470. https://doi.org/10.1016/j.scitotenv.2010.10.053
  41. Tanaka-Kagawa T, Jinno H, Hasegawa T, Makino Y, Seko Y, Hanioka N, et al. Functional characterization of two variant human GSTO 1-1s (Ala140Asp and Thr217Asn). Biochem Biophys Res Commun. 2003; 301(2): 516-520. https://doi.org/10.1016/S0006-291X(02)03066-8
  42. Whitbread AK, Tetlow N, Eyre HJ, Sutherland GR, Board PG. Characterization of the human Omega class glutathione transferase genes and associated polymorphisms. Pharmacogenetics. 2003; 13(3): 131-144. https://doi.org/10.1097/00008571-200303000-00003