Impact of genetic polymorphisms in key enzymes of homocysteine metabolism on the pathophysiology of sickle cell anemia
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.10164/j.freeradbiomed.2017.02.019 http://hdl.handle.net/11449/165601 |
Resumo: | 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. |
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Impact of genetic polymorphisms in key enzymes of homocysteine metabolism on the pathophysiology of sickle cell anemiaHemoglobin SMethylenetetrahydrofolate reductaseCystathionine beta-synthaseHydroxycarbamideThis 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.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)UNESP Sao Paulo State Univ, Dept Biol, Hemoglobin & Hematol Genet Dis Lab, Cristovao Colombo St 2265, Sao Paulo, BrazilUNESP Sao Paulo State Univ, Dept Chem & Environm Sci, Sao Paulo, BrazilHematol State Inst Arthur de Siqueira Cavalcanti, Rio De Janeiro, BrazilFundacao Univ Reg Blumenau, Dept Nat Sci, Blumenau, SC, BrazilUNESP Sao Paulo State Univ, Dept Biol, Hemoglobin & Hematol Genet Dis Lab, Cristovao Colombo St 2265, Sao Paulo, BrazilUNESP Sao Paulo State Univ, Dept Chem & Environm Sci, Sao Paulo, BrazilCNPq: 140911/2011-1FAPESP: 2013/07937-8Elsevier B.V.Universidade Estadual Paulista (Unesp)Hematol State Inst Arthur de Siqueira CavalcantiFundacao Univ Reg BlumenauHumberto da Silva, Danilo Grunig [UNESP]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 deAlmeida, Eduardo Alves de [UNESP]Bonini-Domingos, Claudia Regina [UNESP]2018-11-28T11:22:56Z2018-11-28T11:22:56Z2017-05-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article53-61application/pdfhttp://dx.doi.org/10.10164/j.freeradbiomed.2017.02.019Free Radical Biology And Medicine. New York: Elsevier Science Inc, v. 106, p. 53-61, 2017.0891-5849http://hdl.handle.net/11449/16560110.10164/j.freeradbiomed.2017.02.019WOS:000400724500005WOS000400724500005.pdf32794280661767190000-0002-4603-9467Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFree Radical Biology And Medicine2,178info:eu-repo/semantics/openAccess2024-01-17T06:24:49Zoai:repositorio.unesp.br:11449/165601Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T23:13:29.590941Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Impact of genetic polymorphisms in key enzymes of homocysteine metabolism on the pathophysiology of sickle cell anemia |
title |
Impact of genetic polymorphisms in key enzymes of homocysteine metabolism on the pathophysiology of sickle cell anemia |
spellingShingle |
Impact of genetic polymorphisms in key enzymes of homocysteine metabolism on the pathophysiology of sickle cell anemia Humberto da Silva, Danilo Grunig [UNESP] Hemoglobin S Methylenetetrahydrofolate reductase Cystathionine beta-synthase Hydroxycarbamide |
title_short |
Impact of genetic polymorphisms in key enzymes of homocysteine metabolism on the pathophysiology of sickle cell anemia |
title_full |
Impact of genetic polymorphisms in key enzymes of homocysteine metabolism on the pathophysiology of sickle cell anemia |
title_fullStr |
Impact of genetic polymorphisms in key enzymes of homocysteine metabolism on the pathophysiology of sickle cell anemia |
title_full_unstemmed |
Impact of genetic polymorphisms in key enzymes of homocysteine metabolism on the pathophysiology of sickle cell anemia |
title_sort |
Impact of genetic polymorphisms in key enzymes of homocysteine metabolism on the pathophysiology of sickle cell anemia |
author |
Humberto da Silva, Danilo Grunig [UNESP] |
author_facet |
Humberto da Silva, Danilo Grunig [UNESP] 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] |
author_role |
author |
author2 |
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] |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Hematol State Inst Arthur de Siqueira Cavalcanti Fundacao Univ Reg Blumenau |
dc.contributor.author.fl_str_mv |
Humberto da Silva, Danilo Grunig [UNESP] 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] |
dc.subject.por.fl_str_mv |
Hemoglobin S Methylenetetrahydrofolate reductase Cystathionine beta-synthase Hydroxycarbamide |
topic |
Hemoglobin S Methylenetetrahydrofolate reductase Cystathionine beta-synthase Hydroxycarbamide |
description |
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. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-05-01 2018-11-28T11:22:56Z 2018-11-28T11:22:56Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.10164/j.freeradbiomed.2017.02.019 Free Radical Biology And Medicine. New York: Elsevier Science Inc, v. 106, p. 53-61, 2017. 0891-5849 http://hdl.handle.net/11449/165601 10.10164/j.freeradbiomed.2017.02.019 WOS:000400724500005 WOS000400724500005.pdf 3279428066176719 0000-0002-4603-9467 |
url |
http://dx.doi.org/10.10164/j.freeradbiomed.2017.02.019 http://hdl.handle.net/11449/165601 |
identifier_str_mv |
Free Radical Biology And Medicine. New York: Elsevier Science Inc, v. 106, p. 53-61, 2017. 0891-5849 10.10164/j.freeradbiomed.2017.02.019 WOS:000400724500005 WOS000400724500005.pdf 3279428066176719 0000-0002-4603-9467 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Free Radical Biology And Medicine 2,178 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
53-61 application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier B.V. |
publisher.none.fl_str_mv |
Elsevier B.V. |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129500340289536 |