TY - JOUR T1 - Combined and differential effects of alpha-thalassemia and HbF-quantitative trait loci in Senegalese hydroxyurea-free children with sickle cell anemia. AU - Gueye Tall,Fatou, AU - Martin,Cyril, AU - Ndour,El Hadji Malick, AU - Renoux,Céline, AU - Ly,Indou Déme, AU - Connes,Philippe, AU - Gueye,Papa Madieye, AU - Diallo,Rokhaya Ndiaye, AU - Diagne,Ibrahima, AU - Diop,Pape Amadou, AU - Cissé,Aynina, AU - Lopez Sall,Philomène, AU - Joly,Philippe, Y1 - 2019/07/19/ PY - 2019/03/15/received PY - 2019/06/16/revised PY - 2019/07/07/accepted PY - 2019/7/20/pubmed PY - 2020/2/6/medline PY - 2019/7/20/entrez KW - G6PD deficiency KW - HbF QTL KW - Senegal haplotype KW - alpha-thalassemia KW - genetic modifiers KW - sickle cell anemia SP - e27934 EP - e27934 JF - Pediatric blood & cancer JO - Pediatr Blood Cancer VL - 66 IS - 10 N2 - 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. SN - 1545-5017 UR - https://www.unboundmedicine.com/medline/citation/31322815/Combined_and_differential_effects_of_alpha_thalassemia_and_HbF_quantitative_trait_loci_in_Senegalese_hydroxyurea_free_children_with_sickle_cell_anemia_ DB - PRIME DP - Unbound Medicine ER -