Genetic and biochemical markers of hydroxyurea therapeutic response in sickle cell anemia

dc.contributorUniversidade Estadual Paulista (Unesp)
dc.contributorFaculdade de Medicina de São José do Rio Preto (FAMERP)
dc.contributorHematol State Inst Arthur de Siqueira Cavalcanti
dc.creatorHumberto Silva, Danilo Grunig [UNESP]
dc.creatorBelini Junior, Edis [UNESP]
dc.creatorSouza Carrocini, Gisele Cristine de [UNESP]
dc.creatorTorres, Lidiane de Souza [UNESP]
dc.creatorRicci Junior, Octavio
dc.creatorCastro Lobo, Clarisse Lopes de
dc.creatorBonini-Domingos, Claudia Regina [UNESP]
dc.creatorAlmeida, Eduardo Alves de [UNESP]
dc.date2014-12-03T13:07:09Z
dc.date2014-12-03T13:07:09Z
dc.date2013-10-09
dc.date.accessioned2023-09-09T09:36:19Z
dc.date.available2023-09-09T09:36:19Z
dc.identifierhttp://dx.doi.org/10.1186/1471-2350-14-108
dc.identifierBmc Medical Genetics. London: Biomed Central Ltd, v. 14, 9 p., 2013.
dc.identifier1471-2350
dc.identifierhttp://hdl.handle.net/11449/111293
dc.identifier10.1186/1471-2350-14-108
dc.identifierWOS:000325794000001
dc.identifierWOS000325794000001.pdf
dc.identifier6713400866382255
dc.identifier3279428066176719
dc.identifier0000-0002-4603-9467
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8760972
dc.descriptionBackground: Sickle cell anemia (SCA) presents a complex pathophysiology which can be affected by a number of modifying factors, including genetic and biochemical ones. In Brazil, there have been no studies verifying beta(S)-haplotypes effect on oxidative stress parameters. This study evaluated beta(S)-haplotypes and Hb F levels effects on oxidative stress markers and their relationship with hydroxyurea (HU) treatment in SCA patients.Methods: The studied group was composed by 28 SCA patients. Thirteen of these patients were treated with HU and 15 of them were not. We used molecular methodology (PCR-RFLP) for hemoglobin S genotype confirmation and haplotypes identification. Biochemical parameters were measured using spectrophotometric methods (Thiobarbituric-acid-reactive substances and Trolox equivalent antioxidant capacity levels, catalase and GST activities) and plasma glutathione levels by High-performance liquid chromatography coupled to electrochemical detection.Results: We found the highest frequency of Bantu haplotype (48.2%) which was followed by Benin (32.1%). We observed also the presence of Cameroon haplotype, rare in Brazilian population and 19.7% of atypical haplotypes. The protective Hb F effect was confirmed in SCA patients because these patients showed an increase in Hb F levels that resulted in a 41.3% decrease on the lipid peroxidation levels (r=-0.74, p=0.01). Other biochemical parameters have not shown differential expression according to patient's haplotypes. Bantu haplotype presence was related to the highest lipid peroxidation levels in patients (p<0,01), but it also conferred a differential response to HU treatment, raising Hb F levels in 52.6% (p=0.03) when compared with the group with the same molecular profile without HU usage.Conclusions: SCA patients with Bantu haplotype showed the worst oxidative status. However these patients also demonstrated a better response to the treatment with HU. Such treatment seems to have presented a haplotype-dependent pharmacological effect.
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionMinistry of Health
dc.descriptionSao Paulo State Univ, Dept Biol, Hemoglobin & Hematol Genet Dis Lab, UNESP, Sao Paulo, Brazil
dc.descriptionSao Jose do Rio Preto Med Sch FAMERP, Dept Med, Sao Paulo, Brazil
dc.descriptionHematol State Inst Arthur de Siqueira Cavalcanti, HEMORIO, Rio De Janeiro, Brazil
dc.descriptionSao Paulo State Univ, Dept Chem & Environm Sci, UNESP, Sao Paulo, Brazil
dc.descriptionSao Paulo State Univ, Dept Biol, Hemoglobin & Hematol Genet Dis Lab, UNESP, Sao Paulo, Brazil
dc.descriptionSao Paulo State Univ, Dept Chem & Environm Sci, UNESP, Sao Paulo, Brazil
dc.descriptionCNPq: 409691/2006-2
dc.descriptionFAPESP: 06/03873-1
dc.descriptionMinistry of HealthMS 3072/2007
dc.format9
dc.languageeng
dc.publisherBiomed Central Ltd.
dc.relationBmc Medical Genetics
dc.relation1.913
dc.relation1,109
dc.rightsAcesso aberto
dc.sourceWeb of Science
dc.subjectHemoglobin S
dc.subjectBeta-S-gene cluster haplotypes
dc.subjectOxidative stress
dc.subjectAntioxidant capacity
dc.titleGenetic and biochemical markers of hydroxyurea therapeutic response in sickle cell anemia
dc.typeArtigo


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