Haptoglobin genotypes in sickle cell diseases

Abstract

The pathophysiology of sickle cell disease (SCD) is centered on the polymerization property of the desoxy-hemoglobin (Hb) S, but genetic factors can act as modulators of its clinical complications. Some of the genetic modulators are well known, as the presence of the alpha thalassemia and fetal hemoglobin (HbF) levels. Moreover, several othergenetic polymorphisms have been investigated, such as haptoglobin (Hp) polymorphism. Haptoglobin (Hp) is a plasma glycoprotein whose primary function is to bind to free hemoglobin, preventing excretion of iron by the kidneys and protecting blood vessels from its oxidative effects. It is also an acute phase positive protein with immunomodulatory capacity. Two codominant alleles, HP1 and HP2, result in 3 main genotypes/phenotypes, Hp1-1, Hp2-1 and Hp2-2, which correspond to proteins with different functional characteristics. Several studies have demonstrated that the anti- oxidative efficiency is the genotype/phenotype Hp1-1. Recently, it has been suggested that the Hp2-2 genotype frequency reduces with age in SCD patients and that this reduction may be associated with a worse prognosis. In a previous study developed by our research group, the population analyzed was very expressive (n=775), but was not ideal to be considered as representative of SCD patients as a whole yet. Thus , the aim of this project is to determine the frequencies of Hp genotypesin 200 patients with SCD (SS, SC and Sb-thalassemia) followed at Blood Center of Pernambuco - HEMOPE, subdivided by age groups, including children and adults, in order to obtain the representative sample size of SCD patients. The Hp genotyping will be performed by selective amplification of different Hp alleles by Polymerase Chain Reaction (PCR).