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The effect of vitamin D pathway genes and deferasirox pharmacogenetics on liver iron in thalassaemia major patients

The Pharmacogenomics Journal volume 19, pages 417–427 (2019)Cite this article

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Abstract

Monitoring and treating iron overload is crucial in transfusion-dependent thalassaemia patients. Liver stiffness measurement by transient elastography and T2* magnetic resonance imaging represent non-invasive ways to evaluate the adequacy of the iron chelation treatment. We explored the role of single nucleotide polymorphisms involved in vitamin D metabolism, transport and activity, and in deferasirox metabolism on liver iron burden parameters. One-hundred and five beta-thalassaemia patients, treated with deferasirox, have been enrolled. Drug plasma Ctrough and AUC were measured by a HPLC-UV method. Allelic discrimination was performed by real-time PCR. Age, UGT1A1-364 CT/TT and CYP27B1 -1260 GT/TT positively predicted liver stiffness values. Deferasirox dose and serum ferritin negatively predicted T2* data, whereas age and CYP2D6 1457 GG genotype positively influenced these values. The discoveries of this research may be useful for personalized medicine and the proposed method could be applied in patients with hereditary hemochromatosis and myelodysplastic syndromes.

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Acknowledgements

The authors thank CoQuaLab (www.coqualab.it) for its methodological support and assistance in the preparation and execution of the pharmacogenetic analysis.

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  1. These authors contributed equally: Antonio Piga, Antonio D'Avolio

Authors and Affiliations

  1. Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149, Turin, Italy

    Sarah Allegra, Jessica Cusato, Valeria Avataneo, Amedeo De Nicolò & Antonio D’Avolio

  2. Department of Biological and Clinical Sciences, University of Turin, S. Luigi Gonzaga Hospital, 10043, Orbassano, TO, Italy

    Silvia De Francia & Elisa Pirro

  3. Department of Paediatrics, Centre for Microcitemie, University of Turin, S. Luigi Gonzaga Hospital, 10043, Orbassano, TO, Italy

    Filomena Longo, Davide Massano & Antonio Piga

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  1. Sarah Allegra
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Allegra, S., Cusato, J., De Francia, S. et al. The effect of vitamin D pathway genes and deferasirox pharmacogenetics on liver iron in thalassaemia major patients. Pharmacogenomics J 19, 417–427 (2019). https://doi.org/10.1038/s41397-019-0071-7

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