title: Association between the genetic polymorphisms of glutathione S-transferase (GSTM1 and GSTT1) and the clinical manifestations in sickle cell anemia.
abstract: The hereditary deficiency of antioxidant enzymes when associated with sickle cell anemia (SCA) further contributes to the oxidation of hemoglobin S, which increases the formation of degradation products of this hemoglobin. The glutathione S transferases play an important role in the conjugation of glutathione to endogenous products of peroxidation of lipids and protect cells from the deleterious effects of oxidative stress. We analyzed genomic DNA from 278 patients with sickle cell anemia to correlate the genotypes GSTT1 and/or GSTM1 null (determined by multiplex PCR technique) and the clinical manifestations of the disease. 27% of patients showed absence of the GSTM1 gene and 15% had absence of GSTT1. The GSTM1 and GSTT1 null genotypes were found in 11% of the population. The risk of individuals with the GSTT1 null genotype developing acute chest syndrome and aseptic necrosis of the femoral head were, respectively, 10 and 6.3 times higher when compared with those individuals who had of this gene. Patients with GSTM1 null showed a risk 3.9 times higher to develop stroke and high risk for malleolar ulcers and acute chest syndrome (OR=6.9 and 4.2, respectively). The individuals with the GSTM1 and GSTT1 null genotypes showed a higher chance of developing acute chest syndrome, malleolar ulcer and aseptic necrosis of the femoral head. The absence of GSTT1 and/or GSTM1 was an important risk factor for increasing the morbidity of SCA, especially in regard to acute chest syndrome.
authors.affiliation: Laboratory of Immunopathology Keizo Asami, Federal University of Pernambuco, Recife -PE, Brazil.
authors.forename: Romério Alencar
authors.initials: RA
authors.lastname: de Oliveira Filho
authors.forename: Géssyka Jerônimo
authors.initials: GJ
authors.lastname: Silva
authors.forename: Igor
authors.initials: I
authors.lastname: de Farias Domingos
authors.forename: Betânia Lucena Domingues
authors.initials: BL
authors.lastname: Hatzlhofer
authors.forename: Aderson
authors.initials: A
authors.lastname: da Silva Araújo
authors.forename: José Luiz
authors.initials: JL
authors.lastname: de Lima Filho
authors.forename: Marcos André Cavalcanti
authors.initials: MA
authors.lastname: Bezerra
authors.forename: Danyelly Bruneska Gondim
authors.initials: DB
authors.lastname: Martins
authors.forename: Rosângela Ferreira Frade
authors.initials: RF
authors.lastname: de Araújo
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D018450:Disease Progression; D017353:Gene Deletion; D056726:Genetic Association Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D005982:Glutathione Transferase; C413545:glutathione S-transferase T1