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Combined and differential effects of alpha‐thalassemia and HbF‐quantitative trait loci in Senegalese hydroxyurea‐free children with sickle cell anemia
- Source :
- Pediatric Blood and Cancer, Pediatric Blood and Cancer, Wiley, 2019, 66 (10), pp.e27934. ⟨10.1002/pbc.27934⟩
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- International audience; BACKGROUND: Our objective was to investigate the combined and differential effects of alpha-thalassemia -3.7 kb deletion and HbF-promoting quantitative trait loci (HbF-QTL) in Senegalese hydroxyurea (HU)-free children and young adults with sickle cell anemia (SCA).PROCEDURE: Steady-state biological parameters and vaso-occlusive crises (VOC) requiring emergency admission were recorded over a 2-year period in 301 children with SCA. The age of the first hospitalized VOC was also recorded. These data were correlated with the alpha-globin and HbF-QTL genotypes. For the latter, three different genetic loci were studied (XmnI, rs7482144; BCL11A, rs1427407; and the HBS1L-MYB region, rs28384513) and a composite score was calculated, ranging from zero (none of these three polymorphisms) to six (all three polymorphisms at the homozygous state).RESULTS: A positive clinical impact of the HbF-QTL score on VOC rate, HbF, leucocytes, and C-reactive protein levels was observed only for patients without alpha-thalassemia deletion. Conversely, combination of homozygous -3.7 kb deletion with three to six HbF-QTL was associated with a higher VOC rate. The age of the first hospitalized VOC was delayed for patients with one or two alpha-thalassemia deletions and at least two HbF-QTL.CONCLUSION: Alpha-thalassemia -3.7 kb deletion and HbF-QTL are modulating factors of SCA clinical severity that interact with each other. They should be studied and interpreted together and not separately, at least in HU-free children.
- Subjects :
- Male
congenital, hereditary, and neonatal diseases and abnormalities
medicine.medical_specialty
Genotype
Composite score
Quantitative Trait Loci
Anemia, Sickle Cell
Alpha-thalassemia
Quantitative trait locus
Gastroenterology
[SCCO]Cognitive science
03 medical and health sciences
0302 clinical medicine
sickle cell anemia
alpha-Thalassemia
G6PD deficiency
hemic and lymphatic diseases
Internal medicine
Humans
Medicine
Clinical severity
HbF QTL
Young adult
Child
Fetal Hemoglobin
Hemoglobin H
business.industry
Hematology
Senegal haplotype
genetic modifiers
medicine.disease
Differential effects
Senegal
Sickle cell anemia
3. Good health
Oncology
030220 oncology & carcinogenesis
Pediatrics, Perinatology and Child Health
Female
business
030215 immunology
Subjects
Details
- ISSN :
- 15455017 and 15455009
- Database :
- OpenAIRE
- Journal :
- Pediatric Blood & Cancer
- Accession number :
- edsair.doi.dedup.....9a78e092b5c6fc59fdca261f986a19fd