MDR1 diplotypes as prognostic markers in multiple myeloma.
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.
Maggini
Valentina
V
Department of Biology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Pisa, Italy. vmaggini@biologia.unipi.it
Buda
Gabriele
G
Martino
Alessandro
A
Presciuttini
Silvano
S
Galimberti
Sara
S
Orciuolo
Enrico
E
Barale
Roberto
R
Petrini
Mario
M
Rossi
Anna Maria
AM
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
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005819:Genetic Markers