4.6 Article

Genetic polymorphisms in glutathione S-transferase (GST) superfamily and arsenic metabolism in residents of the Red River Delta, Vietnam

Journal

TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 242, Issue 3, Pages 352-362

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2009.11.007

Keywords

Arsenic; Glutathione S-transferase omega 1 (GST01); GST omega 2 (GSTO2); GST pi 1 (GSTP1); GST mu 1 (GSTM1); GST 01 (GSTT1); Genetic polymorphism; Vietnam

Funding

  1. Japan Society for the Promotion of Science (JSPS)
  2. Vietnamese Academy of Science and Technology (VAST)
  3. Research Revolution [RR2002]
  4. Project for Sustainable Coexistence of Human, Nature and the Earth [FY2002]
  5. JSPS [20221003, 19209025, 207871]
  6. Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan
  7. Grants-in-Aid for Scientific Research [19209025, 20221003] Funding Source: KAKEN

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To elucidate the role of genetic factors in arsenic metabolism, we investigated associations of genetic polymorphisms in the members of glutathione S-transferase (GST) superfamily with the arsenic concentrations in hair and urine, and urinary arsenic profile in residents in the Red River Delta, Vietnam. Genotyping was conducted for CST omega 1 (GSTO1) A1a140Asp, Glu155del, Glu208Lys, Thr217Asn, and Ala236Val, GST omega 2 (GSTO2) Asn142Asp, CST pi 1 (GSTP1) Ile105Val, GST mu 1 (GSTM1) wild/null, and GST theta 1 (GSTT1) wild/null. There were no mutation alleles for GSTO1 Glu208Lys, Thr217Asn, and Ala236Val in this population. GSTO1 Glu 155del hetero type showed higher urinary concentration of As-V than the wild homo type. Higher percentage of DMA(V) in urine of GSTM1 wild type was observed compared with that of the null type. Strong correlations between GSTP1 Ile105Val and arsenic exposure level and profile were observed in this study. Especially, heterozygote of GSTP1 Ile105Val had a higher metabolic capacity from inorganic arsenic to monomethyl arsenic, while the opposite trend was observed for ability of metabolism from As-V to As-III. Furthermore, other factors including sex, age, body mass index, arsenic level in drinking water, and genotypes of As (+ 3 oxidation state) methyltransferase (AS3MT) were also significantly co-associated with arsenic level and profile in the Vietnamese. To our knowledge, this is the first study indicating the associations of genetic factors of CST superfamily with arsenic metabolism in a Vietnamese population. (C) 2009 Elsevier Inc. All rights reserved.

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