title: Impact of genetic polymorphisms in key enzymes of homocysteine metabolism on the pathophysiology of sickle cell anemia.
abstract: This work aimed at studying a possible influence of methylenetetrahydrofolate reductase (MTHFR; c. 677C>T) and cystathionine β-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 5mg/day, while 41 (43.2%) of them were under hydroxycarbamide (HC) treatment (average dose: 22mg/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.
authors.affiliation: UNESP - Sao Paulo State University, Department of Biology, Hemoglobin and Hematologic Genetic Diseases Laboratory, Sao Paulo, Brazil; UNESP - Sao Paulo State University, Department of Chemistry and Environmental Sciences, Sao Paulo, Brazil. Electronic address: dangrunig@gmail.com.
authors.forename: Danilo Grünig Humberto
authors.initials: DGH
authors.lastname: da Silva
authors.affiliation: UNESP - Sao Paulo State University, Department of Biology, Hemoglobin and Hematologic Genetic Diseases Laboratory, Sao Paulo, Brazil.
authors.forename: Edis
authors.initials: E
authors.lastname: Belini Junior
authors.affiliation: UNESP - Sao Paulo State University, Department of Biology, Hemoglobin and Hematologic Genetic Diseases Laboratory, Sao Paulo, Brazil.
authors.forename: Lidiane
authors.initials: L
authors.lastname: de Souza Torres
authors.affiliation: UNESP - Sao Paulo State University, Department of Biology, Hemoglobin and Hematologic Genetic Diseases Laboratory, Sao Paulo, Brazil.
authors.forename: Jessika Viviani
authors.initials: JV
authors.lastname: Okumura
authors.affiliation: UNESP - Sao Paulo State University, Department of Biology, Hemoglobin and Hematologic Genetic Diseases Laboratory, Sao Paulo, Brazil.
authors.forename: Willian
authors.initials: W
authors.lastname: Marcel Barberino
authors.affiliation: UNESP - Sao Paulo State University, Department of Biology, Hemoglobin and Hematologic Genetic Diseases Laboratory, Sao Paulo, Brazil.
authors.forename: Renan
authors.initials: R
authors.lastname: Garcia de Oliveira
authors.affiliation: UNESP - Sao Paulo State University, Department of Biology, Hemoglobin and Hematologic Genetic Diseases Laboratory, Sao Paulo, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Urbinatti Teixeira
authors.affiliation: Hematological State Institute "Arthur de Siqueira Cavalcanti" - HEMORIO, Rio de Janeiro, Brazil.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Lopes de Castro Lobo
authors.affiliation: UNESP - Sao Paulo State University, Department of Chemistry and Environmental Sciences, Sao Paulo, Brazil; FURB - Fundação Universidade Regional de Blumenau, Department of Natural Sciences, Santa Catarina, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Alves de Almeida
authors.affiliation: UNESP - Sao Paulo State University, Department of Biology, Hemoglobin and Hematologic Genetic Diseases Laboratory, Sao Paulo, Brazil.
authors.forename: Claudia Regina
authors.initials: CR
authors.lastname: Bonini-Domingos
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002648:Child; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D005838:Genotype; D006710:Homocysteine / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D006710:Homocysteine; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003541:Cystathionine beta-Synthase
keywords: Cystathionine β-synthase; Hemoglobin S; Hydroxycarbamide; Methylenetetrahydrofolate reductase