title: MDR1 diplotypes as prognostic markers in multiple myeloma.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Pisa, Italy. vmaggini@biologia.unipi.it
authors.forename: Valentina
authors.initials: V
authors.lastname: Maggini
authors.forename: Gabriele
authors.initials: G
authors.lastname: Buda
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martino
authors.forename: Silvano
authors.initials: S
authors.lastname: Presciuttini
authors.forename: Sara
authors.initials: S
authors.lastname: Galimberti
authors.forename: Enrico
authors.initials: E
authors.lastname: Orciuolo
authors.forename: Roberto
authors.initials: R
authors.lastname: Barale
authors.forename: Mario
authors.initials: M
authors.lastname: Petrini
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Rossi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016019:Survival Analysis
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005819:Genetic Markers