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1.
BMC Med Genet ; 14: 108, 2013 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-24106994

RESUMEN

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 ßS-haplotypes effect on oxidative stress parameters. This study evaluated ßS-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.


Asunto(s)
Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/genética , Hidroxiurea/uso terapéutico , Adolescente , Adulto , Anciano , Anemia de Células Falciformes/patología , Biomarcadores/metabolismo , Niño , Femenino , Hemoglobina Fetal/análisis , Estudios de Seguimiento , Genotipo , Glutatión/sangre , Haplotipos , Hemoglobina Falciforme/genética , Humanos , Peroxidación de Lípido , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Fenotipo , Espectrofotometría , Adulto Joven
3.
Rev. bras. hematol. hemoter ; 33(3): 231-236, June 2011. tab
Artículo en Inglés | LILACS | ID: lil-596327

RESUMEN

Human hemoglobin genes are located in α and β globin gene clusters in chromosomes 16 and 11, respectively. Different types of hemoglobin are synthesized according to the stage of development with fetal hemoglobin (α2γ2) (Hb F) being the main hemoglobin in the fetal period. After birth, there is a reduction (to about 1 percent) in Hb F levels and adult hemoglobin, Hb A (2α2β2), increases to more than 96 percent of total hemoglobin. However, some genetic conditions whether linked to the β-globin gene cluster or not are associated with high Hb F levels in adults. Among those linked to β-globin are hereditary persistence of fetal hemoglobin, delta-beta thalassemia (δβ-Thalassemia) and the XmnI polymorphism (-158 C > T). Other polymorphisms not related to β-globin gene cluster are known to influence the γ-globin gene expression in adulthood. The most relevant polymorphisms that increase concentrations of Hb F are the HMIP locus on chromosome 6, the BCL11A locus on chromosome 2, the Xp22.2 region of the X chromosome and the 8q region on chromosome 8. Findings from our research group studying genetic factors involved in γ-globin gene regulation in adults without anemia in the northwestern region of São Paulo State showed that high Hb F levels are influenced by the presence of hereditary persistence of fetal hemoglobin mutations and the XmnI polymorphism, suggesting that both genetic alterations characterize the molecular basis of the evaluated population.


Asunto(s)
Humanos , Hemoglobina Fetal , Polimorfismo Genético
4.
Rev Bras Hematol Hemoter ; 33(3): 231-6, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-23049301

RESUMEN

Human hemoglobin genes are located in α and ß globin gene clusters in chromosomes 16 and 11, respectively. Different types of hemoglobin are synthesized according to the stage of development with fetal hemoglobin (α(2)γ(2)) (Hb F) being the main hemoglobin in the fetal period. After birth, there is a reduction (to about 1%) in Hb F levels and adult hemoglobin, Hb A (2α(2)ß(2)), increases to more than 96% of total hemoglobin. However, some genetic conditions whether linked to the ß-globin gene cluster or not are associated with high Hb F levels in adults. Among those linked to ß-globin are hereditary persistence of fetal hemoglobin, delta-beta thalassemia (δß-Thalassemia) and the XmnI polymorphism (-158 C = T). Other polymorphisms not related to ß-globin gene cluster are known to influence the γ-globin gene expression in adulthood. The most relevant polymorphisms that increase concentrations of Hb F are the HMIP locus on chromosome 6, the BCL11A locus on chromosome 2, the Xp22.2 region of the X chromosome and the 8q region on chromosome 8. Findings from our research group studying genetic factors involved in γ-globin gene regulation in adults without anemia in the northwestern region of São Paulo State showed that high Hb F levels are influenced by the presence of hereditary persistence of fetal hemoglobin mutations and the XmnI polymorphism, suggesting that both genetic alterations characterize the molecular basis of the evaluated population.

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