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Environ Health Perspect. 2003 August; 111(11): 1421–1427.
PMCID: PMC1241635
Research Article

Genetic variation in genes associated with arsenic metabolism: glutathione S-transferase omega 1-1 and purine nucleoside phosphorylase polymorphisms in European and indigenous Americans.

Abstract

Individual variability in human arsenic metabolism has been reported frequently in the literature. This variability could be an underlying determinant of individual susceptibility to arsenic-induced disease in humans. Recent analysis revealing familial aggregation of arsenic metabolic profiles suggests that genetic factors could underlie interindividual variation in arsenic metabolism. We screened two genes responsible for arsenic metabolism, human purine nucleoside phosphorylase (hNP), which functions as an arsenate reductase converting arsenate to arsenite, and human glutathione S-transferase omega 1-1 (hGSTO1-1), which functions as a monomethylarsonic acid (MMA) reductase, converting MMA(V) to MMA(III), to develop a comprehensive catalog of commonly occurring genetic polymorphisms in these genes. This catalog was generated by DNA sequencing of 22 individuals of European ancestry (EA) and 24 individuals of indigenous American (IA) ancestry. In (Italic)hNP(/Italic), 48 polymorphic sites were observed, including 6 that occurred in exons, of which 1 was nonsynonymous (G51S). One intronic polymorphism occurred in a known enhancer region. In hGSTO1-1, 33 polymorphisms were observed. Six polymorphisms occurred in exons, of which 4 were nonsynonymous. In contrast to hNP, in which the IA group was more polymorphic than the EA group, in hGSTO1-1 the EA group was more polymorphic than the IA group, which had only 1 polymorphism with a frequency > 10%. Populations representing genetic admixture between the EA and IA groups, such as Mexican Hispanics, could vary in the extent of polymorphism in these genes based upon the extent of admixture. These data provide a framework in which to conduct genetic association studies of these two genes in relevant populations, thereby allowing hNP and hGSTO1-1 to be evaluated as potential susceptibility genes in human arsenicism.

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Selected References

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  • Abernathy CO, Liu YP, Longfellow D, Aposhian HV, Beck B, Fowler B, Goyer R, Menzer R, Rossman T, Thompson C, et al. Arsenic: health effects, mechanisms of actions, and research issues. Environ Health Perspect. 1999 Jul;107(7):593–597. [PMC free article] [PubMed]
  • Asmuss M, Mullenders LH, Hartwig A. Interference by toxic metal compounds with isolated zinc finger DNA repair proteins. Toxicol Lett. 2000 Mar 15;112-113:227–231. [PubMed]
  • Bates MN, Smith AH, Hopenhayn-Rich C. Arsenic ingestion and internal cancers: a review. Am J Epidemiol. 1992 Mar 1;135(5):462–476. [PubMed]
  • Board PG, Coggan M, Chelvanayagam G, Easteal S, Jermiin LS, Schulte GK, Danley DE, Hoth LR, Griffor MC, Kamath AV, et al. Identification, characterization, and crystal structure of the Omega class glutathione transferases. J Biol Chem. 2000 Aug 11;275(32):24798–24806. [PubMed]
  • Cerda-Flores Ricardo M, Villalobos-Torres Maria C, Barrera-Saldaña Hugo A, Cortés-Prieto Lizette M, Barajas Leticia O, Rivas Fernando, Carracedo Angel, Zhong Yixi, Barton Sara A, Chakraborty Ranajit. Genetic admixture in three Mexican Mestizo populations based on D1S80 and HLA-DQA1 loci. Am J Hum Biol. 2002 Mar-Apr;14(2):257–263. [PubMed]
  • Chen F, Vallyathan V, Castranova V, Shi X. Cell apoptosis induced by carcinogenic metals. Mol Cell Biochem. 2001 Jun;222(1-2):183–188. [PubMed]
  • Chung Joyce S, Kalman David A, Moore Lee E, Kosnett Michael J, Arroyo Alex P, Beeris Martin, Mazumder D N Guha, Hernandez Alexandra L, Smith Allan H. Family correlations of arsenic methylation patterns in children and parents exposed to high concentrations of arsenic in drinking water. Environ Health Perspect. 2002 Jul;110(7):729–733. [PMC free article] [PubMed]
  • Devlin B, Risch N. A comparison of linkage disequilibrium measures for fine-scale mapping. Genomics. 1995 Sep 20;29(2):311–322. [PubMed]
  • Ewing B, Hillier L, Wendl MC, Green P. Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res. 1998 Mar;8(3):175–185. [PubMed]
  • Gordon D, Abajian C, Green P. Consed: a graphical tool for sequence finishing. Genome Res. 1998 Mar;8(3):195–202. [PubMed]
  • Hunter ES., 3rd Role of oxidative damage in arsenic-induced teratogenesis. Teratology. 2000 Oct;62(4):240–240. [PubMed]
  • Jonsson JJ, Converse A, McIvor RS. An enhancer in the first intron of the human purine nucleoside phosphorylase-encoding gene. Gene. 1994 Mar 25;140(2):187–193. [PubMed]
  • Jonsson JJ, Foresman MD, Wilson N, McIvor RS. Intron requirement for expression of the human purine nucleoside phosphorylase gene. Nucleic Acids Res. 1992 Jun 25;20(12):3191–3198. [PMC free article] [PubMed]
  • Jonsson JJ, Williams SR, McIvor RS. Sequence and functional characterization of the human purine nucleoside phosphorylase promoter. Nucleic Acids Res. 1991 Sep 25;19(18):5015–5020. [PMC free article] [PubMed]
  • Kirkpatrick DS, Dale KV, Catania JM, Gandolfi AJ. Low-level arsenite causes accumulation of ubiquitinated proteins in rabbit renal cortical slices and HEK293 cells. Toxicol Appl Pharmacol. 2003 Jan 15;186(2):101–109. [PubMed]
  • Kitchin KT. Recent advances in arsenic carcinogenesis: modes of action, animal model systems, and methylated arsenic metabolites. Toxicol Appl Pharmacol. 2001 May 1;172(3):249–261. [PubMed]
  • Kong Augustine, Gudbjartsson Daniel F, Sainz Jesus, Jonsdottir Gudrun M, Gudjonsson Sigurjon A, Richardsson Bjorgvin, Sigurdardottir Sigrun, Barnard John, Hallbeck Bjorn, Masson Gisli, et al. A high-resolution recombination map of the human genome. Nat Genet. 2002 Jul;31(3):241–247. [PubMed]
  • Laliberte Ronald E, Perregaux David G, Hoth Lise R, Rosner Philip J, Jordan Crystal K, Peese Kevin M, Eggler James F, Dombroski Mark A, Geoghegan Kieran F, Gabel Christopher A. Glutathione s-transferase omega 1-1 is a target of cytokine release inhibitory drugs and may be responsible for their effect on interleukin-1beta posttranslational processing. J Biol Chem. 2003 May 9;278(19):16567–16578. [PubMed]
  • Markert ML. Purine nucleoside phosphorylase deficiency. Immunodefic Rev. 1991;3(1):45–81. [PubMed]
  • Nickerson DA, Tobe VO, Taylor SL. PolyPhred: automating the detection and genotyping of single nucleotide substitutions using fluorescence-based resequencing. Nucleic Acids Res. 1997 Jul 15;25(14):2745–2751. [PMC free article] [PubMed]
  • Radabaugh Timothy R, Sampayo-Reyes Adriana, Zakharyan Robert A, Aposhian H Vasken. Arsenate reductase II. Purine nucleoside phosphorylase in the presence of dihydrolipoic acid is a route for reduction of arsenate to arsenite in mammalian systems. Chem Res Toxicol. 2002 May;15(5):692–698. [PubMed]
  • Rutherford K, Parkhill J, Crook J, Horsnell T, Rice P, Rajandream MA, Barrell B. Artemis: sequence visualization and annotation. Bioinformatics. 2000 Oct;16(10):944–945. [PubMed]
  • Sato T, Wakabayashi Y. [PNP deficiency]. Ryoikibetsu Shokogun Shirizu. 1998;(21 Pt 2):228–231. [PubMed]
  • Stephens M, Smith NJ, Donnelly P. A new statistical method for haplotype reconstruction from population data. Am J Hum Genet. 2001 Apr;68(4):978–989. [PubMed]
  • Styblo M, Del Razo LM, LeCluyse EL, Hamilton GA, Wang C, Cullen WR, Thomas DJ. Metabolism of arsenic in primary cultures of human and rat hepatocytes. Chem Res Toxicol. 1999 Jul;12(7):560–565. [PubMed]
  • Tanaka-Kagawa Toshiko, Jinno Hideto, Hasegawa Tatsuya, Makino Yuko, Seko Yoshiyuki, Hanioka Nobumitsu, Ando Masanori. Functional characterization of two variant human GSTO 1-1s (Ala140Asp and Thr217Asn). Biochem Biophys Res Commun. 2003 Feb 7;301(2):516–520. [PubMed]
  • Thomas DJ, Styblo M, Lin S. The cellular metabolism and systemic toxicity of arsenic. Toxicol Appl Pharmacol. 2001 Oct 15;176(2):127–144. [PubMed]
  • Tishkoff SA, Pakstis AJ, Ruano G, Kidd KK. The accuracy of statistical methods for estimation of haplotype frequencies: an example from the CD4 locus. Am J Hum Genet. 2000 Aug;67(2):518–522. [PubMed]
  • Vahter M. Methylation of inorganic arsenic in different mammalian species and population groups. Sci Prog. 1999;82(Pt 1):69–88. [PubMed]
  • Vahter M, Couch R, Nermell B, Nilsson R. Lack of methylation of inorganic arsenic in the chimpanzee. Toxicol Appl Pharmacol. 1995 Aug;133(2):262–268. [PubMed]
  • Whitbread Astrid K, Tetlow Natasha, Eyre Helen J, Sutherland Grant R, Board Philip G. Characterization of the human Omega class glutathione transferase genes and associated polymorphisms. Pharmacogenetics. 2003 Mar;13(3):131–144. [PubMed]
  • Wildfang E, Radabaugh TR, Vasken Aposhian H. Enzymatic methylation of arsenic compounds. IX. Liver arsenite methyltransferase and arsenate reductase activities in primates. Toxicology. 2001 Nov 30;168(3):213–221. [PubMed]
  • Yin ZL, Dahlstrom JE, Le Couteur DG, Board PG. Immunohistochemistry of omega class glutathione S-transferase in human tissues. J Histochem Cytochem. 2001 Aug;49(8):983–987. [PubMed]
  • Zakharyan RA, Sampayo-Reyes A, Healy SM, Tsaprailis G, Board PG, Liebler DC, Aposhian HV. Human monomethylarsonic acid (MMA(V)) reductase is a member of the glutathione-S-transferase superfamily. Chem Res Toxicol. 2001 Aug;14(8):1051–1057. [PubMed]

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