Relationship between gene polymorphisms at BCL11A and hemolysis markers in patients with sickle cell disease

Sickle cell disease (SCD) is a hematological disease caused by a point mutation in the β-globin gene. Sickle hemoglobin (HbS) is generated due to fragile mutation that decreases the red blood cell lifetime due to its chronic destruction, being the main responsible for the signs and symptoms of the disease. The use of hydroxyurea (HU) and genetic polymorphisms on modulates fetal hemoglobin (HbF), the main inhibitor of HbS polymerization, reducing hemolysis and vaso-occlusion. This study aimed to evaluate the association of polymorphisms BCL11A gene on the hemolysis markers reticulocytes, bilirubin, uric acid, lactate dehydrogenase (LDH) and methemoglobin (MetHb). The study included 45 patients with SCD of both sexes, in use of HU, attended in outpatient University Hospital Walter Cantídio (HUWC) in Fortaleza, Ceará, and 80 healthy individuals as a control group. The MetHb, uric acid and bilirubin dosage has performed by spectrophotometric method, the LDH by a kinetic method, the reticulocyte count by manual method and evaluation of BCL11A polymorphisms by PCR in real time. Data were analyzed using the statistical software GraphPad Prism. The level of significance was set at <5%. Patients with SCD and healthy subjects showed a difference between hematological parameters, hemoglobin, hematocrit, mean corpuscular volume (MCV) and platelets. Regarding the hemolysis parameters, it was observed that SCD patients has an increase of reticulocytes, MetHb, LDH and bilirubins compared to control group. The rs7557939 region showed an association with hemolysis biomarkers MetHb and LDH and rs4671393 region with the HbS concentration. The use of HU at doses higher than 10 mg/kg/day and for a longer period than 50 months had association with the decrease of the LDH concentration and the reticulocyte count. We conclude that polymorphisms on BCL11A gene and treatment with HU may modulate the hemolysis biomarkers, however, more research is necessary to study prognostic indicators and the factors involved in the clinical heterogeneity of SCD.A anemia falciforme (AF) é uma doença hematológica causada por uma mutação pontual no gene da β-globina. A hemoglobina S (HbS) gerada devido à mutação forma hemácias com menor meia-vida devido à sua destruição crônica, sendo a principal responsável pelos sinais e sintomas da doença. Os polimorfismos do gene BLC11A e o uso de hidroxiuréia (HU) modulam a concentração de hemoglobina fetal (HbF), principal inibidora da polimerização da HbS, diminuindo a hemólise e a vaso-oclusão. O presente estudo teve o objetivo de associar os polimorfismos do gene BCL11A com os biomarcadores de hemólise reticulócitos, bilirrubinas, ácido úrico, lactato desidrogenase (LDH), e metemoglobina (MetHb). Participaram do estudo 45 pacientes com AF em uso de HU, de ambos os sexos, atendidos no ambulatório de Hematologia do Hospital Universitário Walter Cantídio (HUWC) em Fortaleza-Ceará e 80 indivíduos saudáveis como grupo controle. A dosagem de MetHb, de ácido úrico e bilirrubinas foi realizada através de método espectrofotométrico, a de LDH por método cinético, a contagem de reticulócitos por metodologia manual e a avaliação dos polimorfismos do BCL11A por PCR em tempo real. Os dados obtidos foram analisados utilizando-se o programa estatístico GraphPad Prism. O nível de significância foi estabelecido em