HbF-promoting polymorphisms may specifically reduce the residual risk of cerebral vasculopathy in SCA children with alpha-thalassemia

Philippe Joly (1) , Nathalie Bonello-Palot (2, 3) , Catherine Badens (2, 3) , Serge Pissard (4) , Abdourahim Chamouine (5) , Françoise Bernaudin (6) , Yves Bertrand (7) , Philippe Connes (1) , Céline Renoux (1)

1 LIBM - Laboratoire Interuniversitaire de Biologie de la Motricité
2 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
3 Centre de Référence des Syndromes Drépanocytaires Majeurs, Thalassémies et Autres pathologies rares du globule rouge et de l’Erythropoïèse
4 Hôpital Henri Mondor
5 Centre Hospitalier de Mayotte
6 CHIC - Centre Hospitalier Intercommunal de Créteil
7 IHOPe - Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL]

Sickle cell anemia (SCA) is a disease characterized by abnormal red blood cell rheology. Because of their effects on HbS polymerization and red blood cell deformability, alpha-thalassemia and the residual HbF level are known genetic modifiers of the disease. The aim of our study was to determine if the number of HbF quantitative trait loci (QTL) would also favor a specific sub-phenotype of SCA as it is the case for alpha-thalassemia. Our results confirmed that alpha-thalassemia protected from cerebral vasculopathy but increased the risk for frequent painful vaso-occlusive crises. We also showed that more HbF-QTL may provide an additional and specific protection against cerebral vasculopathy but only for children with alpha-thalassemia (-α/αα or -α/-α genotypes).

Domaines: Génétique; Médecine humaine et pathologie

Philippe Joly, Nathalie Bonello-Palot, Catherine Badens, Serge Pissard, Abdourahim Chamouine, et al.. HbF-promoting polymorphisms may specifically reduce the residual risk of cerebral vasculopathy in SCA children with alpha-thalassemia. Clinical Hemorheology and Microcirculation, 2021, 77 (3), pp.267-272. ⟨10.3233/CH-200951⟩. ⟨hal-03662455⟩