PLEIOTROPIC EFFECT OF POLYMORPHISMS IN THE BCL11A GENE IN INDIVIDUALS WITH SICKLE CELL ANEMIA

Abstract

Sickle cell anemia (SCA) is one of the types of sickle cell disease (SCD), which is characterized by hematological events such as hemolysis and endothelial damage that culminate in vaso-occlusion, leading to the appearance of several clinical manifestations. SCD is the result of erythrocyte alteration conditioned by a mutation in the HBB gene that leads to the formation of hemoglobin S (HbS). Fetal hemoglobin (HbF) is known to positively affect the clinical condition of individuals with SCA, by interfering with the role of HbS in erythrocyte alteration. Genetic polymorphisms are known to positively modulate clinical phenotypes of SCD, with the BCL11A gene being an important marker in this regard. However, polymorphisms in the BCL11A gene have been described as negatively change the clinical status of patients with SCD. The aim of this present study was associate laboratory biomarkers in the presence of polymorphisms rs766432 (C>A) and rs6732518 (C>T) in the BCL11A gene. Hematological and biochemical markers were investigated by automated methods and genetic markers were identified by polymerase chain reaction and Restriction Fragment Length Polymorphism (PCR-RFLP) techniques. Statistical analyses were performed using the GraphPad Prism software, version 9.0. HbF showed a statistically significant association in the presence of the rs766432 polymorphism (p = 0.0306) as well as simultaneously with the rs6732518 polymorphism (p = 0.0302), and HbS concentration (p = 0.0464). The concentration of hemoglobin (Hb) (p = 0.0008), hematocrit (Ht) (p = 0.0243) (p = 0.0329) and red blood cell count (RBC) (p = 0.0069) (p = 0.00466) were high in the presence of polymorphisms. Total (p = 0.0264) and direct (p = 0.0039) bilirubin concentration showed lower values in the presence of the rs766432 polymorphism, as well as in the co-inheritance of both polymorphisms (p = 0.0073) (p = 0. 0154). High concentrations of HDL cholesterol were associated with the presence of the variant allele of the polymorphism rs766432 (p = 0.0402) and high levels of alpha1-antitrypsin were associated with the presence of the variant allele of the polymorphism rs6732518 (p = 0.0320). There was no correlation between HbF and HDL (r = 0.03705). It is concluded that polymorphisms in the BCL11A locus are important for the variation in HbF levels, and that they may have a pleiotropic effect by determining laboratory parameters not related thus hemoglobin.