Genetic modifiers of fetal hemoglobin affect the course of sickle cell disease in patients treated with hydroxyurea
| Title: | Genetic modifiers of fetal hemoglobin affect the course of sickle cell disease in patients treated with hydroxyurea |
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| 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 |
| Source: | Haematologica, Vol 107, Iss 7 (2021) |
| Publisher Information: | Ferrata Storti Foundation, 2021. |
| Publication Year: | 2021 |
| Collection: | LCC:Diseases of the blood and blood-forming organs |
| Subject Terms: | Diseases of the blood and blood-forming organs, RC633-647.5 |
| More Details: | The course of sickle cell disease (SCD) is modified by polymorphisms boosting fetal hemoglobin (HbF) synthesis. However, it has remained an open question how these polymorphisms affect patients who are treated with the HbF-inducing drug hydroxyurea/ hydroxycarbamide. The German SCD registry offers the opportunity to answer this question, because >90% of patients are treated according to national guidelines recommending the use of hydroxyurea in all patients above 2 years of age. We analyzed the modifying effect of HbF-related genetic polymorphisms in 417 patients with homozygous SCD >2 years old who received hydroxyurea. HbF levels were correlated with higher total hemoglobin levels, lower rates of hemolysis, a lower frequency of painful crises and of red blood cell transfusions. The minor alleles of the polymorphisms in the γ-globin promoter (rs7482144), BCL11A (rs1427407) and HMIP (rs66650371) were strongly associated with increased HbF levels. However, these associations did not translate into lower frequencies of vaso-occlusive events which did not differ between patients either carrying or not carrying the HMIP and BCL11A polymorphisms. Patients on hydroxyurea carrying the γ-globin promoter polymorphism demonstrated substantially higher hemoglobin levels (P |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 0390-6078 1592-8721 |
| Relation: | https://haematologica.org/article/view/10440; https://doaj.org/toc/0390-6078; https://doaj.org/toc/1592-8721 |
| DOI: | 10.3324/haematol.2021.278952 |
| Access URL: | https://doaj.org/article/6917040d732d4b14a269d5e926b9d34b |
| Accession Number: | edsdoj.6917040d732d4b14a269d5e926b9d34b |
| Database: | Directory of Open Access Journals |
| ISSN: | 03906078 15928721 |
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| DOI: | 10.3324/haematol.2021.278952 |
| Published in: | Haematologica |
| Language: | English |