Abstract
Hematopoietic stem cell transplantation(HSCT)has emerged as a curative strategy for sickle cell anemia(SCA); it is necessary to find markers of SCA clinical severity to spare those SCA patients whose clinical course is mild from the morbidity and mortality associated with HSCT. Haplotypes have been correlated with the severity of clinical manifestations in SCA patients, and fetal hemoglobin(HbF)and socioeconomic status(SeS)have also been described as negative factors. We studied these factors and their impact on clinical manifestations in a population of Southern Brazilian patients attending the Center for Sickle Cell Anemia at Hospital de Clinicas de Porto Alegre/RS, Brazil. Clinical severity was defined as two or more veno-occlusive episodes per year. The βS haplotypes were determined by PCR in 75 SCA patients. Among the 150 βS chromosomes analyzed, 99(66%)were identified as Bantu(Ban), 41(27%)asBenin(Ben), and 10(7%)as other haplotypes. Most patients in our sample(62.7%)belonged to lower SeS groups, precluding meaningful statistical analysis of SeS impact on clinical severity. There was no correlation between haplotypes or HbF level and SCA clinical severity. Gene polymorphisms and environmental issues have to be taken into consideration.
Highlights
Sickle mutation of the beta-globin locus, which in the homozygous state gives rise to sickle cell anemia (SCA), is caused by the substitution of an adenine (A) for a thymine (T) in the sixth codon of the beta-globin gene, leading to the substitution of glutamic acid for valine and to the production of hemoglobin S (HbS) [1] [2]
There was no significant correlation between HbF levels and genotype or clinical severity (Table 1 and Table 2)
Our data corroborate the prevalence of Bantu haplotypes among Afro-Brazilians, which is consistent with the origins of the African slaves brought to Brazil during the slave trade
Summary
Sickle mutation of the beta-globin locus, which in the homozygous state gives rise to sickle cell anemia (SCA), is caused by the substitution of an adenine (A) for a thymine (T) in the sixth codon of the beta-globin gene, leading to the substitution of glutamic acid for valine and to the production of hemoglobin S (HbS) [1] [2]. HbS polymerizes under low oxygen tension (hypoxia), producing the characteristic sickle-shaped erythrocytes [3]. This event leads to hemolysis that promotes adhesive properties of circulating cells and the vessel wall. Reticulocyte adherence provides an additional link between hemolytic anemia and vaso-occlusion [4], which is the hallmark of SCA. These important pathophysiological aspects of SCA trigger painful events and contribute largely to the morbidity and mortality associated with the disease [5]. Some studies have suggested that SCA is a chronic inflammatory disease, with clinical manifestations being influenced by an inflammatory state which contributes to vaso-occlusive events and appears to play an important role in the pathophysiology of the disease [6]-[8]
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