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

Article type: Research Article

Authors: Joly, Philippe^{a; b; c; *} | Bonello-Palot, Nathalie^d | Badens, Catherine^d | Pissard, Serge^e | Chamouine, Abdourahim^f | Bernaudin, Françoise^g | Bertrand, Yves^h | Connes, Philippe^{a; b; c} | Renoux, Céline^{a; b; c}

Affiliations: [a] Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Equipe “Biologie Vasculaire et du Globule Rouge”, Université Claude Bernard Lyon 1, COMUE Lyon, France | [b] Laboratoire d’Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France | [c] UF “Biochimie des Pathologies Érythrocytaires”, Laboratoire de Biochimie et Biologie Moléculaire Grand-Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France | [d] Centre de Référence Maladies Rares du Globule Rouge, Laboratoire de Génétique Moléculaire, Hôpital de la Timone, APHM, Aix Marseille Université, INSERM, MMG, Marseille, France | [e] Département de Génétique Moléculaire, Hôpital Mondor, AP-HP et UPEC-IMRB U9552, Créteil, France | [f] Service de Pédiatrie, Centre Hospitalier de Mayotte, Mamoudzou, France | [g] Centre de Référence de la Drépanocytose, Centre Hospitalier Inter-Communal de Créteil, Créteil, France | [h] Institut d’Hématologie et d’Oncologie Pédiatrique, Lyon, France

Correspondence: [*] Corresponding author: Dr. Philippe Joly. E-mail: philippe.joly@chu-lyon.fr.

Abstract: 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).

Keywords: SCA, HbF quantitative trait loci, XmnI, BCL11A, HBS1L-MYB, cerebral vasculopathy, alpha-globin genotype

DOI: 10.3233/CH-200951

Journal: Clinical Hemorheology and Microcirculation, vol. 77, no. 3, pp. 267-272, 2021