Impact of genetic polymorphisms in key enzymes of homocysteine metabolism on the pathophysiology of sickle cell anemia

• Main Author: Humberto da Silva, Danilo Grunig [UNESP]
• Publication Date: 2017
• Other Authors: Belini Junior, Edis [UNESP], Torres, Lidiane de Souza [UNESP], Okumura, Jessika Viviani [UNESP], Barberino, Willian Marcel [UNESP], Oliveira, Renan Garcia de [UNESP], Teixeira, Vanessa Urbinatti [UNESP], Castro Lobo, Clarisse Lopes de, Almeida, Eduardo Alves de [UNESP], Bonini-Domingos, Claudia Regina [UNESP]
• Format: Article
• Language: eng
• Source: Repositório Institucional da UNESP
• Download full: http://dx.doi.org/10.10164/j.freeradbiomed.2017.02.019; http://hdl.handle.net/11449/165601
• topic: Hemoglobin S; Methylenetetrahydrofolate reductase; Cystathionine beta-synthase; Hydroxycarbamide

This work aimed at studying a possible influence of methylenetetrahydrofolate reductase (MTHFR; C. 677C > T) and cystathionine beta-synthase (CBS; 844ins68) polymorphisms on overall oxidative status of sickle cell anemia (SCA) patients and on routine markers, correlating them with hydroxycarbamide (HC) treatment. We evaluated 95 unrelated and diagnosed SCA patients. All patients received a prophylactic treatment with folic acid of 5 mg/day, while 41 (43.2%) of them were under hydroxycarbamide (HC) treatment (average dose: 22 mg/kg/day). MTHFR and CBS polymorphisms were identified by Polymerase Chain Reaction. Biochemical parameters were measured using spectrophotometric and chromatographic methods. Routine markers were developed by specialized laboratory. We did not find any effect of 677T and I allele combination on the biomarkers evaluated. On the other hand, MTHFR 677T mutation was related to a depletion of antioxidant capacity, according to the decreased catalase activity and a reduction about 30% of glutathione levels. Moreover, the presence of the insertion was related to about 23% less biomolecule oxidation levels and lower monocytes count, but about 14% higher lactate dehydrogenase activity. These findings may contribute to highlight that the MTHFR and CBS polymorphisms involvement in SCA pathophysiology is likely to be far more complex than it was explored to date.