Author(s): Lima, Brena de Lourdes Aguiar
Date: 2015
Origin: Oasisbr
Subject(s): Polimorfismos; Glutationa S-Transferase; Mal??ria - Plasmodium Vivax; Polymorphisms; Glutathione S-transferase; Susceptibility; Vivax malaria; Severity; CI??NCIAS DA SA??DE: FARM??CIA
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CAPES - Coordena????o de Aperfei??oamento de Pessoal de N??vel Superior
Plasmodium vivax threatens ~40% of the world s population, with a wide spectrum of asymptomatic to severe clinical manifestations. Glutathione S-transferase (GST) gene polymorphisms have been shown to influence their ability to reduce oxidative stress. Using molecular tools we identified and compared GSTM1, GSTT1 and GSTP1 gene polymorphism in 175 uncomplicated (n=118) and severe (n=57) vivax patients. There were no differences in the frequency of GST alleles between uncomplicated and severe malaria. Nevertheless, a comparison of biochemical and hematological parameters in severe malaria, we observed patients with GSTM1 double-deletion had more platelets (p<0.04) suggesting a decreased risk of thrombocytopenia. In addition, patients with single and/or double deletion of GSTT1 and GSTM1 also had a reduced risk for thrombocytopenia (p<0.045, p<0.026, respectively) compared to wild type allele. In contrast, individuals with GSTP1 heterozygous or homozygous A313G mutation had an increased risk of jaundice (p<0.034, p<0.022) and anemia as observed with decreased RBCs (p<0.008), hemoglobin (p<0.019) and hematocrit (p<0.008) levels in serum. Our results, not only indicate a direct influence of GST polymorphism on biochemical parameters but also its diagnostic potential in assessing disease progression during clinical malaria.
Plasmodium vivax acomete aproximadamente 40% da popula????o mundial, com um amplo espectro de manifesta????es cl??nicas, desde formas assintom??ticas a infec????es graves. Polimorfismos nos genes da Glutationa S-transferase (GST) influenciam a capacidade das isoenzimas de reduzir o estresse oxidativo. Usando m??todos moleculares n??s identificamos e comparamos polimorfismos nos genes da GST em 175 pacientes com mal??ria vivax n??o-grave (n=118) e grave (n=57). N??o houve diferen??as estat??sticas nas freq????ncias al??licas das GSTs entre os pacientes com mal??ria n??o grave e grave. No entanto, guando comparou-se os par??metros bioqu??micos e hematol??gicos no grupo com mal??ria grave, observamos que pacientes com dele????o no gene GSTM1 apresentaram maior contagem plaquet??ria (p??0.04), sugerindo menor risco de trombocitopenia. Al??m disso, pacientes com dele????o ??nica e/ou dupla nos genes GSTT1 e GSTM1 demonstraram menor risco de desenvolverem trombocitopenia (p??0.045, p??0.026, respectivamente) em compara????o com os pacientes portadores do gen??tipo selvagem. Em contraste, indiv??duos com mal??ria grave e portadores dos gen??tipos heterozigotos ou homozigotos para a muta????o A313G no gene GSTP1 apresentaram maior risco de desenvolverem icter??cia (p??0.034, p??0.022, respectivamente) e anemia, como demonstrado pelos menores n??veis de hem??cias (p??0.008, p??0.019, respectivamente) e hemat??crito (p??0.008). Nossos resultados n??o indicam apenas uma influ??ncia direta dos polimorfismos das GSTs nos par??metros bioqu??micos e hematol??gicos, mas tamb??m o seu potencial de avaliar a progress??o da doen??a.
