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

Autor(es)

Humberto Silva, Danilo Grunig ^{[1, 2]} ; Belini Junior, Edis ^[2] ; de Souza Carrocini, Gisele Cristine ^[2] ; Torres, Lidiane de Souza ^[2] ; Ricci Junior, Octavio ^[3] ; de Castro Lobo, Clarisse Lopes ^[4] ; Bonini-Domingos, Claudia Regina ^[2] ; de Almeida, Eduardo Alves ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, Dept Chem & Environm Sci, UNESP, Sao Paulo - Brazil

^[2] Sao Paulo State Univ, Dept Biol, Hemoglobin & Hematol Genet Dis Lab, UNESP, Sao Paulo - Brazil

^[3] Sao Jose do Rio Preto Med Sch FAMERP, Dept Med, Sao Paulo - Brazil

^[4] Hematol State Inst Arthur de Siqueira Cavalcanti, HEMORIO, Rio De Janeiro - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BMC MEDICAL GENETICS; v. 14, OCT 9 2013.
• Citações Web of Science: 9

Resumo

Background: 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. (AU)

• Processo FAPESP: 06/03873-1 - Estudo de variações bioquímicas em tilápias, como biomarcadores de contaminação ambiental
• Beneficiário: Eduardo Alves de Almeida
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores