Polymorphisms in Glutathione S-transferase genes, Development, and Progression of Sepsis

Author(s): Natália Brito da Cruz, José Gildo de Moura Monteiro Júnior, Dário Celestino Sobral Filho, Dilênia de Oliveira Cipriano Torres, José Luiz de Lima Filho, Danyelly Bruneska Gondim Martins, Rosângela Ferreira Frade de Araújo

Introduction: Sepsis is an inefficient and deleterious inflammatory response from the host against an infectious agent that can lead to organ dysfunction. The oxidative stress is related to the pathogenesis of several high prevalence diseases. Therefore, a better comprehension of the oxidative regulation during sepsis can lead to new therapeutic perspectives. Glutathione S-transferases (GST) is an important antioxidant enzyme system involved in the mechanism of cellular detoxification. So, there has been an increasing interest in the possible pathological implications of the polymorphisms in GST.

Methodology: 116 samples from patients admitted in the cardiovascular ICU were analyzed using PCR multiplex and PCR-RFLP techniques to find possible associations between GSTT1, GSTM1 e GSTP1 polymorphisms and a greater risk of developing sepsis, as well as its worse prognosis.

Results: GSTM1 and GSTT1 null genotypes frequency was, respectively, 26.72% and 13.79% while 7.75% of the patients presented nullity for both genes. GSTP1 genotypic distribution showed a higher percentage for the heterozygous variant genotype. Polymorphisms did not influence the risk of developing sepsis and were also not related to higher APACHE II and SOFA scores.

Conclusions: Despite important studies showed the classes Mu, Pi, and Theta polymorphisms effects in the pathogenesis of several diseases, in this study, there has been no significant association between the studied polymorphisms and sepsis, and its worse prognosis.