Polymorphism in glutathione S-transferase P1 is associated with susceptibility to Plasmodium vivax malaria compared to P falciparum and upregulates the GST level during malarial infection

Glutathione S-transferase P1 (GSTP1) is a member of the GST superfamily which has well-established multiple roles in various infectious and parasitic diseases The genetic regulation of GSTP1 has been extensively studied Thus its biological significance and disease association prompted us to investigate the role of GSTP1 polymorphisms in Plasmodium-mediated pathogenesis in Infected humans The genotypic distribution of IIe105Val in Plasmodium vivax infection was observed to be significant and strongly associated (OR = 4 5) with the progression of pathology whereas in P falciparum infection no significant association was observed compared to healthy subjects Interestingly we observed significant elevation of GST in vivax infection with both genotypes IIe105Val and Va1105Val compared to healthy subjects whereas in P falciparum infection we found marginally elevated GST levels of mutated genotypes but significantly depleted compared to healthy subjects Further during vivax and falciparum infection overall significant elevations of glutathione glutathione peroxidase and GST levels were observed Expression of both GSTP1 mRNA and protein was significantly upregulated during vivax infection compared to falciparum infection and both were significantly upregulated compared to the levels in healthy subjects as well These studies suggest that GSTP1 polymolphism is involved in the pathogenesis of malaria and it may serve as a valuable molecular marker possessing a promising rationale for diagnostic potential in assessing disease progression during clinical malaria (C) 2010 Elsevier Inc All rights reserved