ORIGINAL ARTICLESMDR1 diplotypes as prognostic markers in multiple myelomaMaggini, Valentinaa *; Buda, Gabrieleb *; Martino, Alessandroa; Presciuttini, Silvanoc; Galimberti, Sarab; Orciuolo, Enricob; Barale, Robertoa; Petrini, Mariob; Rossi, Anna MariaaAuthor Information aDepartment of Biology bDepartment of Oncology, Transplants and Advanced Technologies, Section of Hematology cDepartment of Experimental Pathology, Medical Biotechnologies, Infectivology and Epidemiology, Pisa University, Pisa, Italy Correspondence to Dr Valentina Maggini, Department of Biology, Pisa University, Via Derna 1, 56126, Pisa, Italy Tel: +39 050 221 1524; fax: +39 050 221 1527; e-mail: [email protected] *Valentina Maggini and Gabriele Buda contributed equally to this study. Received 5 November 2007 Accepted 14 January 2008 Pharmacogenetics and Genomics: May 2008 - Volume 18 - Issue 5 - p 383-389 doi: 10.1097/FPC.0b013e3282f82297 Buy Metrics Abstract Objective The aim of this study was to evaluate the effect of diplotypes of MDR1 polymorphisms at positions 2677 and 3435 on the clinical outcome of multiple myeloma, in terms of response to the therapy and overall survival (OS). Methods G2677T/A SNP was analysed by RFLP-PCR assay on 110 patients, treated with dexamethasone, doxorubicin (adryamicin) and vincristine regimen, followed by autologous stem cell transplantation. Results Treatment efficacy was not related to G2677T/A SNP, whereas the OS of G/G carriers was significantly shorter than that of T/T or G/T patients. Similar results were previously reported for MDR1 C3435T polymorphism. Given that these two single nucleotide polymorphisms are in strong linkage disequilibrium, we analyzed the effects of the most frequent haplo/diplotypes and the survival probability was lower for GC/GC patients (55%) than for GC/TT and TT/TT carriers (>80%; log-rank test, P=0.03). Interestingly, the effect of MDR1 diplotype on the OS seems to be confined to autologous stem cell transplantation nonresponders. Conclusion These results support the hypothesis that genetic variability of MDR1 should be considered as an important factor that influences the clinical outcome of multiple myeloma. © 2008 Lippincott Williams & Wilkins, Inc.