Role of Genomic Biomarkers in Increasing Fetal Hemoglobin Levels Upon Hydroxyurea Therapy and in β-Thalassemia Intermedia: A Validation Cohort Study.
Title | Role of Genomic Biomarkers in Increasing Fetal Hemoglobin Levels Upon Hydroxyurea Therapy and in β-Thalassemia Intermedia: A Validation Cohort Study. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Kolliopoulou, A., Siamoglou S., John A., Sgourou A., Kourakli A., Symeonidis A., Vlachaki E., Chalkia P., Theodoridou S., Ali B. R., Katsila T., Patrinos G. P., & Papachatzopoulou A. |
Journal | Hemoglobin |
Volume | 43 |
Issue | 1 |
Pagination | 27-33 |
Date Published | 2019 Jan |
ISSN | 1532-432X |
Keywords | Alleles, beta-Globins, beta-Thalassemia, Biomarkers, Female, Fetal Hemoglobin, Genomics, Genotype, Humans, Hydroxyurea, Male, Mutation, Phenotype, Severity of Illness Index, Treatment Outcome |
Abstract | Hemoglobinopathies exhibit a remarkable phenotypic diversity in terms of disease severity, while individual genetic background plays a key role in differential response to drug treatment. In the last decade, genomic variants in genes located within, as well as outside the human β-globin cluster have been shown to be significantly associated with Hb F increase, in relation to hydroxyurea (HU) therapy in patients with these diseases. Here, we aim to determine the effect of genomic variants located in genes, such as , , , , , and , previously shown to modulate fetal hemoglobin (Hb F) levels in patients with β type hemoglobinopathies and reflecting disease severity and response to HU therapy in an independent cohort of Greek patients with these diseases. We recruited and genotyped 45 β-thalassemia patients (β-thal), either transfusion-dependent (TDT) or non transfusion-dependent (NTDT), 42 Hb S (: c.20A>T)-β-thal compound heterozygotes, who were treated with HU, as well as 53 healthy individuals, all of Hellenic origin. Our study showed that genomic variants of the , and gene are associated with HU therapy efficacy in Hb S-β-thal compound heterozygotes. We have also shown that and genomic variants are associated with the mild phenotype of NTDT patients. Our findings provide evidence that , , genomic variants could be considered as genomic biomarkers to predict HU therapy efficacy in Hb S-β-thal compound heterozygotes and also to describe disease severity in patients with β type hemoglobinopathies. |
DOI | 10.1080/03630269.2019.1597732 |
Alternate Journal | Hemoglobin |
PubMed ID | 31039620 |