Abstract
Beta-thalassemia can present with a wide spectrum of phenotypes determined by the coinheritance of α-thalassemia, hereditary persistence of fetal hemoglobin, and polymorphic variants in the BCL11A, HMIP, and HBB clusters. The codon 29 (cd29) mutation in the beta gene has been associated with a broad diversity of thalassemia phenotypes, possibly through genetic modifiers determining the genotype-phenotype relationship. In this study, we evaluated the effect of 10 single nucleotide polymorphisms (SNPs) on β-thalassemia severity in a group of 21 Lebanese patients bearing the cd29 mutation. Hematological parameters and clinical characteristics were evaluated according to transfusion dependence. The proportions and absolute concentrations of HbF were found to be higher in non-transfusion-dependent (NTD) patients than in transfusion-dependent (TD) ones. Iron parameters were found to be higher in TD patients. The SNPs that were evaluated included the XmnI-158 polymorphism in the HBG gene and SNPs in the BCL11A and HMIP loci. It was noted that individuals homozygous or heterozygous for the effect allele in the BCL11A and HMIP SNPs had higher HbF levels, lower ferritin concentrations, and lower liver iron content and were less likely to be transfusion dependent. Our results showed that HbF production variants may have an important impact on the severity of β-thalassemia, which might provide a severity prediction tool that can help in the anticipation of patients’ phenotypes and therefore in future therapeutic decision making.
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Acknowledgments
The authors are grateful to all patients and their families who donated samples for this study.
Funding
This work was partially supported by the Italian Ministry of Health and Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico [RC_2018] to MDC. The following funding was assigned to Ali Taher: Novartis Pharmaceuticals: research funding, honoraria, consultant; Celgene: research funding; La Jolla Pharmaceuticals: research funding; Protagonist Therapeutics: consultant; and Ionis Pharmaceuticals: consultant.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Brancaleoni, V., Moukhadder, H.M., Consonni, D. et al. Common fetal hemoglobin variants in Lebanese patients bearing the codon 29 beta gene mutation associated with different thalassemia phenotypes. Ann Hematol 98, 833–840 (2019). https://doi.org/10.1007/s00277-018-3567-3
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DOI: https://doi.org/10.1007/s00277-018-3567-3