Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad-500016, India; Dr. NTR University of Health Sciences, Vijayawada, A.P., India.
Gene. 2013 Dec 1;531(2):301-5. doi: 10.1016/j.gene.2013.08.078. Epub 2013 Sep 11.
Deferiprone is used as a chelation agent in chronic iron overload in β-thalassemia patients. Patients on deferiprone therapy show variable response to this drug in terms of reduction in iron overload as well as adverse drug reactions (ADRs). The pharmacogenetic studies on deferiprone have not carried out in patients with blood disorders in India. Therefore, the present study was carried out to evaluate the three most common nonsynonymous UGT1A6 polymorphisms Thr181Ala (541 A/G), Arg184Ser (552 A/C) and Ser7Ala (19 T/G) and therapeutic response to deferiprone in β-thalassemia major patients. Two hundred and eighty six (286) β-thalassemia major patients were involved in the study. Serum ferritin levels were estimated periodically to assess the status of the iron overload and the patients were grouped into responders and non-responders depending on the ferritin levels. The UGT1A6 2 polymorphisms were detected by PCR-RFLP methods. The association between the genotypes and outcome as well as ADRs was evaluated by Open EPI software. A significant difference was observed in the genotypic distribution of UGT1A6 2 Thr181Ala polymorphism in responders and non-responders. However, there was no difference in the genotypic distribution between patients with and without ADRs. As far as the UGT1A6 2 Arg184Ser polymorphism is concerned, no significant difference was observed between responders and non-responders. Further, evaluating the association of UGT1A6 2 Ser7Ala polymorphism with drug response, there was no significant difference in the genotypic distribution between responders and non-responders. However, there was a significant difference between responders with and without ADRs and non-responders with and without ADRs. In addition to this haplotype analysis was also carried out. However, we did not find any specific haplotype to be significantly associated with the deferiprone response in β-thalassemia major patients.
地拉罗司被用作β-地中海贫血患者慢性铁过载的螯合剂。接受地拉罗司治疗的患者在减少铁过载和药物不良反应（ADR）方面对地拉罗司的反应各不相同。印度尚未对血液疾病患者进行地拉罗司的遗传药理学研究。因此，本研究旨在评估三个最常见的非同义 UGT1A6 突变 Thr181Ala（541A/G）、Arg184Ser（552A/C）和 Ser7Ala（19T/G）以及地拉罗司在β-地中海贫血患者中的治疗反应。共有 286 名β-地中海贫血患者参与了这项研究。定期评估血清铁蛋白水平以评估铁过载状况，并根据铁蛋白水平将患者分为应答者和非应答者。采用 PCR-RFLP 方法检测 UGT1A6 2 个多态性。采用 Open EPI 软件评估基因型与结果及 ADR 之间的关系。在应答者和非应答者中，UGT1A6 2 Thr181Ala 多态性的基因型分布存在显著差异。然而，在有无 ADR 的患者之间，基因型分布没有差异。至于 UGT1A6 2 Arg184Ser 多态性，应答者和非应答者之间没有观察到显著差异。进一步评估 UGT1A6 2 Ser7Ala 多态性与药物反应的关系，应答者和非应答者之间的基因型分布没有显著差异。然而，在有无 ADR 的应答者和非应答者之间存在显著差异。此外，还进行了单体型分析。然而，我们没有发现任何特定的单体型与β-地中海贫血患者对地拉罗司的反应显著相关。
