Influence of βS-globin haplotypes and hydroxyurea on tumor necrosis factor-alpha levels in sickle cell anemia.
BACKGROUND
Sickle cell anemia is a chronic inflammatory disease characterized by an increased production of proinflammatory cytokines including tumor necrosis factor-alpha. Hydroxyurea, by decreasing the polymerization of hemoglobin, reduces inflammatory states. The effect of the genetic polymorphisms of sickle cell patients on tumor necrosis factor-alpha levels remains unknown.


OBJECTIVE
The aim of this study was to investigate the association of tumor necrosis factor-alpha levels with β-globin haplotypes and the use of hydroxyurea.


METHODS
A cross-sectional study was performed of 67 patients with sickle cell anemia diagnosed at steady-state in a referral hospital in Fortaleza, Ceará, Brazil. A group of 26 healthy individuals was used as control. βS-haplotype analysis was performed by restriction fragment length polymorphism-polymerase chain reaction. The tumor necrosis factor-alpha levels were measured by the enzyme-linked immunosorbent assay test. Laboratory data (complete blood count and fetal hemoglobin) and information regarding the use of hydroxyurea were obtained from medical records. Statistical analysis was performed using R software with the Kruskal-Wallis and Mann-Whitney tests. Statistical significance was established for p-values < 0.05 for all analyses.


RESULTS
The mean age of the participants was 35.48 years. Patients with sickle cell anemia had significantly higher tumor necrosis factor-alpha levels than controls (p-values < 0.0001). Tumor necrosis factor-alpha levels were lower in sickle cell anemia patients who were receiving hydroxyurea treatment than those who were not (p-value = 0.1249). Sickle cell anemia patients with Bantu/n genotype had significantly higher levels than patients with the Bantu/Benin genotype (p-value = 0.0021).


CONCLUSIONS
In summary, βS-globin haplotypes, but not hydroxyurea therapy, have a role in modulating tumor necrosis factor-alpha levels in sickle cell anemia adults at steady-state. Many previous studies have investigated prognosis and inflammatory states in sickle cell anemia patients, but the discovery that tumor necrosis factor-alpha levels vary according to the genetic polymorphism of the patient is a new finding.
Universidade Federal do Ceará, Fortaleza, CE, Brazil, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
Marília Rocha
MR
Laurentino
Universidade Federal do Ceará, Fortaleza, CE, Brazil, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
Pedro Aurio
PA
Maia
Universidade Federal do Ceará, Maranguape, CE, Brazil, Universidade Federal do Ceará (UFC), Maranguape, CE, Brazil.
Maritza Cavalcante
MC
Barbosa
Universidade Federal do Ceará, Fortaleza, CE, Brazil, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
Izabel Cristina Justino
IC
Bandeira
Universidade Federal do Ceará, Fortaleza, CE, Brazil, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
Lilianne Brito da Silva
LB
Rocha
Universidade Federal do Ceará, Fortaleza, CE, Brazil, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
Romelia Pinheiro
RP
Gonçalves
Anemia, sickle cell; Haplotypes; Hydroxyurea; Inflammation; Tumor necrosis factor-alpha