Influence of βS-Globin Haplotypes and Hydroxyurea on Arginase I Levels in Sickle Cell Disease.
Introduction. Sickle cell disease (SCD) is characterized by hemoglobin S homozygosity, leading to hemolysis and vasoocclusion. The hemolysis releases arginase I, an enzyme that decreases the bioavailability of nitric oxide, worsening the symptoms. The different SCD haplotypes are related to clinical symptoms and varied hemoglobin F (HbF) concentration. The aim of this study was to evaluate the impact of the βS gene haplotypes and HbF concentration on arginase I levels in SCD patients. Methods. Fifty SCD adult patients were enrolled in the study and 20 blood donors composed the control group. Arginase I was measured by ELISA. The βS haplotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analyses were performed with GraphPad Prism program and the significance level was p < 0.05. Results. Significant increase was observed in the arginase I levels in SCD patients compared to the control group (p < 0.0001). The comparison between the levels of arginase I in three haplotypes groups showed a difference between the Bantu/Bantu × Bantu/Benin groups; Bantu/Bantu × Benin/Benin, independent of HU dosage. An inverse correlation with the arginase I levels and HbF concentration was observed. Conclusion. The results support the hypothesis that arginase I is associated with HbF concentration, also measured indirectly by the association with haplotypes.
Post-Graduate Program in Pathology, Federal University of Ceará, Rua Capitão Francisco Pedro, 1210 Rodolfo Teófilo, 60430-370 Fortaleza, CE, Brazil.
J A
JA
Moreira
Post-Graduate Program in Development and Technological Innovation in Drugs, Federal University of Ceará, Rua Capitão Francisco Pedro, 1210 Rodolfo Teófilo, 60430-370 Fortaleza, CE, Brazil.
R P G
RP
Machado
Post-Graduate Program in Pathology, Federal University of Ceará, Rua Capitão Francisco Pedro, 1210 Rodolfo Teófilo, 60430-370 Fortaleza, CE, Brazil.
M R
MR
Laurentino
Department of Clinical and Toxicological Analysis, University of Ceará, Rua Capitão Francisco Pedro, 1210 Rodolfo Teófilo, 60430-370 Fortaleza, CE, Brazil.
Romelia Pinheiro Gonçalves
RP
Lemes
Post-Graduate Program in Pharmaceutical Sciences, Federal University of Ceará, Rua Capitão Francisco Pedro, 1210 Rodolfo Teófilo, 60430-370 Fortaleza, CE, Brazil.
M C
MC
Barbosa
Post-Graduate Program in Pharmaceutical Sciences, Federal University of Ceará, Rua Capitão Francisco Pedro, 1210 Rodolfo Teófilo, 60430-370 Fortaleza, CE, Brazil.
T E
TE
Santos
Post-Graduate Program in Pharmaceutical Sciences, Federal University of Ceará, Rua Capitão Francisco Pedro, 1210 Rodolfo Teófilo, 60430-370 Fortaleza, CE, Brazil.
I C J
IC
Bandeira
Department of Clinical and Toxicological Analysis, University of Ceará, Rua Capitão Francisco Pedro, 1210 Rodolfo Teófilo, 60430-370 Fortaleza, CE, Brazil.
A M C
AM
Martins
D000328:Adult; D000755:Anemia, Sickle Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001119:Arginase / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D055544:beta-Globins / Q000235:genetics*
D015415:Biomarkers; D055544:beta-Globins; D001119:Arginase; D006918:Hydroxyurea