Volume 81, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Malaria infection induces oxidative stress in the host cells. Antioxidant enzymes such as glutathione S-transferases (GSTs) are responsible for fighting reactive oxygen species and reduction of oxidative stress. Common GST polymorphisms have been associated with susceptibility to different diseases whose pathologies involve oxidative stress. In this study, we tested the hypothesis that GST polymorphisms that lead to reduced or lack of enzyme activity are associated with severe malarial anemia. We studied the genotypic distribution of , , and polymorphisms between mild malaria ( = 107) and severe malarial anemia ( = 50) in Tanzanian children. We did not find a significant relationship with the polymorphism. -null was higher in the severe malaria anemia group but the difference was not significant ( = 0.08). However, a significant association of I105V genotype with severe malarial anemia was discovered (26.0% against 10.3% mild malaria, = 0.004). We concluded that and possibly may protect against severe falciparum malaria in children.


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  1. Pagola S, Stephens PW, Bohle DS, Kosar AD, Madsen SK, 2000. The structure of malaria pigment beta-haematin. Nature 404 : 307–310. [Google Scholar]
  2. Slater AF, 1993. Chloroquine: mechanism of drug action and resistance in Plasmodium falciparum. Pharmacol Ther 57 : 203–235. [Google Scholar]
  3. Pandey AV, Bisht H, Babbarwal VK, Srivastava J, Pandey KC, Chauhan VS, 2001. Mechanism of malarial haem detoxification inhibition by chloroquine. Biochem J 355 : 333–338. [Google Scholar]
  4. Maitland K, Marsh K, 2004. Pathophysiology of severe malaria in children. Acta Trop 90 : 131–140. [Google Scholar]
  5. Schwarzer E, Turrini F, Giribaldi G, Cappadoro M, Arese P, 1993. Phagocytosis of P. falciparum malarial pigment hemozoin by human monocytes inactivates monocyte protein kinase C. Biochim Biophys Acta 1181 : 51–54. [Google Scholar]
  6. Schwarzer E, Arese P, 1996. Phagocytosis of malarial pigment hemozoin inhibits NADPH-oxidase activity in human monocyte-derived macrophages. Biochim Biophys Acta 1316 : 169–175. [Google Scholar]
  7. Taramelli D, Basilico N, Pagani E, Grande R, Monti D, Ghione M, Olliaro P, 1995. The heme moiety of malaria pigment (beta-hematin) mediates the inhibition of nitric oxide and tumor necrosis factor-alpha production by lipopolysaccharide-stimulated macrophages. Exp Parasitol 81 : 501–511. [Google Scholar]
  8. Becker K, Tilley L, Vennerstrom JL, Roberts D, Rogerson S, Ginsburg H, 2004. Oxidative stress in malaria parasite-infected erythrocytes: host-parasite interactions. Int J Parasitol 34 : 163–189. [Google Scholar]
  9. Ali-Osman F, Akande O, Antoun G, Mao JX, Buolamwini J, 1997. Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants. Evidence for differential catalytic activity of the encoded proteins. J Biol Chem 272 : 10004–10012. [Google Scholar]
  10. Strange RC, Jones PW, Fryer AA, 2000. Glutathione S-transferase: genetics and role in toxicology. Toxicol Lett 112–113 : 357–363. [Google Scholar]
  11. Strange RC, Lear JT, Fryer AA, 1998. Glutathione S-transferase polymorphisms: influence on susceptibility to cancer. Chem Biol Interact 111–112 : 351–364. [Google Scholar]
  12. Kavishe RA, Koenderink JB, McCall MB, Peters WH, Mulder B, Hermsen CC, Sauerwine RW, Russel FG, Van der Ven AJ, 2006. Short report: severe Plasmodium falciparum malaria in Cameroon: associated with the glutathione S-transferase M1 null genotype. Am J Trop Med Hyg 75 : 827–829. [Google Scholar]
  13. Shekalaghe S, Drakeley C, Gosling R, Ndaro A, van Meegeren M, Enevold A, Alifrangis M, Mosha F, Sauerwine R, Bousema T, 2007. Primaquine clears submicroscopic Plasmodium falciparum gametocytes that persist after treatment with sulphadoxine-pyrimethamine and artesunate. PLoS Clin Trials 2 : e1023. [Google Scholar]
  14. Marsh K, Forster D, Waruiru C, Mwangi I, Winstanley M, Marsh V, Newton C, Winstanley P, Peshu N, et al., 1995. Indicators of life-threatening malaria in African children. N Engl J Med 332 : 1399–1404. [Google Scholar]
  15. Molyneux ME, Taylor TE, Wirima JJ, Borgstein A, 1989. Clinical features and prognostic indicators in pediatric cerebral malaria: a study of 131 comatose Malawian children. Q J Med 71 : 441–459. [Google Scholar]
  16. Pemble S, Schroeder KR, Spencer SR, Meyer DJ, Hallier E, Bolt HM, et al., 1994. Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 300 : 271–276. [Google Scholar]
  17. Bröckmoller J, Kerb R, Drakoulis N, Nitz M, Roors I, 1993. Genotype and phenotype of glutathione S-transferase class isoenzymes and psi in lung cancer patients and controls. Lung Cancer 10 : 273. [Google Scholar]
  18. Watson MA, Stewart RK, Smith GBJ, Massey TE, Bell DA, 1998. Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis 19 : 275–280. [Google Scholar]
  19. Mcglynn KA, Rosvold EA, Lustbader ED, Hu Y, Clapper ML, Zhou TL, et al., 1995. Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B-1. Proc Natl Acad Sci USA 92 : 2384–2387. [Google Scholar]
  20. Mukanganyama S, Masimirembwa CM, Naik YS, Hasler JA, 1997. Phenotyping of the glutathione S-transferase M1 polymorphism in Zimbabweans and the effects of chloroquine on blood glutathione S-transferases M1 and A. Clin Chim Acta 265 : 145–155. [Google Scholar]
  21. Rossini A, Rapozo DC, Amorim LM, Macedo JM, Medina R, Neto JF, Gallo CV, Pinto LF, 2002. Frequencies of GSTM1, GSTT1, and GSTP1 polymorphisms in a Brazilian population. Genet Mol Res 1 : 233–240. [Google Scholar]
  22. Tiemersma EW, Omer RE, Bunschoten A, van’t Veer P, Kok FJ, Idris MO, Kadaru AM, Fedail SS, Kampman E, 2001. Role of genetic polymorphism of glutathione-S-transferase T1 and microsomal epoxide hydrolase in aflatoxin-associated hepatocellular carcinoma. Cancer Epidemiol Biomarkers Prev 10 : 785–791. [Google Scholar]
  23. Zhao L, Alldersea J, Fryer A, Tighe A, Ollier B, Thomson W, Jones P, Strange R, 1994. Polymorphism at the glutathione S-transferase GSTM1 locus: a study of the frequencies of the GSTM1-A, B, A/B and null phenotypes in Nigerians. Clin Chim Acta 225 : 85–88. [Google Scholar]
  24. Schneider J, Bernges U, Philipp M, Woitowitz HJ, 2004. GSTM1, GSTT1, and GSTP1 polymorphism and lung cancer risk in relation to tobacco smoking. Cancer Lett 208 : 65–74. [Google Scholar]
  25. Hu X, Xia H, Srivastava SK, Herzog C, Awasthi YC, Ji XH, Zimniak P, Singh SV, 1997. Activity of four allelic forms of glutathione S-transferase hGSTP1-1 for diol epoxides of polycyclic aromatic hydrocarbons. Biochem Biophys Res Commun 238 : 397–402. [Google Scholar]
  26. Sundberg K, Johansson AS, Stenberg G, Widersten M, Seidel A, Mannervik B, Jernström B, 1998. Differences in the catalytic efficiencies of allelic variants of glutathione transferase P1-1 towards carcinogenic diol epoxides of polycyclic aromatic hydrocarbons. Carcinogenesis 19 : 433–436. [Google Scholar]
  27. Wang LH, Groves MJ, Hepburn MD, Bowen DT, 2000. Glutathione S-transferase enzyme expression in hematopoietic cell lines implies a differential protective role for T1 and A1 isoenzymes in erythroid and for M1 in lymphoid lineages. Haematologica 85 : 573–579. [Google Scholar]
  28. Famin O, Krugliak M, Ginsburg H, 1999. Kinetics of inhibition of glutathione-mediated degradation of ferriprotoporphyrin IX by antimalarial drugs. Biochem Pharmacol 58 : 59–68. [Google Scholar]
  29. Ginsburg H, Famin O, Zhang JM, Krugliak M, 1998. Inhibition of glutathione-dependent degradation of heme by chloroquine and amodiaquine as a possible basis for their antimalarial mode of action. Biochem Pharmacol 56 : 1305–1313. [Google Scholar]
  30. Deharo E, Barkan D, Krugliak M, Golenser J, Ginsburg H, 2003. Potentiation of the antimalarial action of chloroquine in rodent malaria by drugs known to reduce cellular glutathione levels. Biochem Pharmacol 66 : 809–817. [Google Scholar]

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  • Received : 27 Nov 2008
  • Accepted : 18 Apr 2009

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