Pleiotropic Effects of Polymorphisms in the BCL11A Gene on Laboratory Parameters in Sickle Cell Anemia

TL;DR

This study explores how genetic variations in the BCL11A gene affect blood markers in sickle cell anemia patients, including fetal hemoglobin and other lab parameters.

Contribution

The study identifies pleiotropic effects of BCL11A polymorphisms on multiple laboratory parameters in sickle cell anemia.

Findings

Elevated HbF levels are significantly associated with rs766432 and rs6732518 polymorphisms.

High HDL is linked to rs766432, and elevated alpha-1antitrypsin to rs6732518.

No correlation was found between HbF and HDL concentrations.

Abstract

Sickle cell anemia (SCA) is characterized by hematological events that lead to vaso-occlusion and the onset of clinical manifestations. Fetal hemoglobin (HbF) has been shown to positively influence the clinical outcomes of individuals with SCA. Genetic polymorphisms are known to modulate clinical phenotypes by increasing HbF levels, with the BCL11A gene being an important marker in this regard for future therapies. However, while the BCL11A gene plays a role in the regulation of several genes during hematopoiesis, its various effects are not yet fully understood. The study aimed to investigate association between laboratory biomarkers in the presence of rs766432 and rs6732518 polymorphisms in the BCL11A gene. Hematological and biochemical markers were analyzed using automated methods, while genetic markers were identified by PCR-RFLP techniques. Elevated HbF levels were significantly associated with the presence of rs766432 and rs6732518 polymorphisms. High concentrations of HDL were associated with rs766432 polymorphism, and elevated levels of alpha-1antitrypsin were linked to the rs6732518 polymorphism. No correlation was found between HbF and HDL concentrations. The low sample size represents a major constraint, making the results only suggestive. In conclusion, polymorphisms in the BCL11A gene are important for variations in HbF levels and may have a pleiotropic effect by influencing laboratory parameters unrelated to HbF levels.

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