Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149, Turin, Italy.
Department of Biological and Clinical Sciences, University of Turin, S. Luigi Gonzaga Hospital, 10043, Orbassano, TO, Italy.
Pharmacogenomics J. 2019 Oct;19(5):417-427. doi: 10.1038/s41397-019-0071-7. Epub 2019 Jan 17.
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 C 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.
监测和治疗铁过载对依赖输血的地中海贫血患者至关重要。瞬态弹性成像和 T2磁共振成像的肝硬度测量是评估铁螯合治疗效果的非侵入性方法。我们探讨了维生素 D 代谢、转运和活性以及地拉罗司代谢中涉及的单核苷酸多态性在肝铁负荷参数中的作用。我们招募了 105 名接受地拉罗司治疗的β-地中海贫血患者。采用 HPLC-UV 法测定药物血浆 C 和 AUC。实时 PCR 进行等位基因鉴别。年龄、UGT1A1-364 CT/TT 和 CYP27B1-1260 GT/TT 阳性预测肝硬度值。地拉罗司剂量和血清铁蛋白负预测 T2数据，而年龄和 CYP2D6 1457 GG 基因型则对这些值有积极影响。这项研究的发现可能对个体化医学有用，所提出的方法可应用于遗传性血色素沉着症和骨髓增生异常综合征患者。
