Fatou Gueye Tall1,2,3, Cyril Martin2,4, El Hadji Malick Ndour1,3, Céline Renoux2,5, Indou Déme Ly3,6, Philippe Connes2,4,7, Papa Madieye Gueye1, Rokhaya Ndiaye Diallo1, Ibrahima Diagne6,8, Pape Amadou Diop1, Aynina Cissé1, Philomène Lopez Sall1,3, Philippe Joly2,4,5. 1. Laboratoire de Biochimie Pharmaceutique-FMPO, Université Cheikh Anta Diop, Dakar, Sénégal. 2. Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Equipe "Biologie vasculaire et du globule rouge", Université Claude Bernard Lyon 1, COMUE, Lyon, France. 3. Centre Hospitalier National d'Enfants Albert Royer, Dakar, Sénégal. 4. Laboratoire d'Excellence sur le globule rouge (Labex GR-Ex), Paris, France. 5. UF "Biochimie des pathologies érythrocytaires", Laboratoire de Biochimie et Biologie moléculaire Grand-Est, Groupement hospitalier Est, Hospices Civils de Lyon, Bron, France. 6. Service universitaire de Pédiatrie-FMPO, Université Cheikh Anta Diop, Dakar, Sénégal. 7. Institut Universitaire de France, Paris, France. 8. UFR des sciences de la santé - Université Gaston Berger, Saint-Louis, Sénégal.
Abstract
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.
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.
Authors: Pierre Allard; Nareen Alhaj; Stephan Lobitz; Holger Cario; Andreas Jarisch; Regine Grosse; Lena Oevermann; Dani Hakimeh; Laura Tagliaferri; Elisabeth Kohne; Annette Kopp-Schneider; Andreas E Kulozik; Joachim B Kunz Journal: Haematologica Date: 2022-07-01 Impact factor: 11.047
Authors: Mariana Delgadinho; Catarina Ginete; Brígida Santos; Armandina Miranda; Miguel Brito Journal: Int J Environ Res Public Health Date: 2021-05-19 Impact factor: 3.390