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| Status |
Public on Nov 23, 2016 |
| Title |
A Genome Wide Association Study Reveals Genetic Predisposition for Bortezomib-Induced Peripheral Neuropathy in Multiple Myeloma by Variation in the PREP1-CBS locus. |
| Organism |
Homo sapiens |
| Experiment type |
SNP genotyping by SNP array
Genome variation profiling by SNP array
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| Summary |
We performed a genome-wide association study using Affymetrix HD-SNP arrays 6.0 to identify risk variants for developing bortezomib-induced peripheral neuropathy (BiPN) in 469 multiple myeloma (MM) patients who received bortezomib-dexamethasone (VD) induction therapy prior to autologous stem-cell transplantation (ASCT) and conducted validation in an independent cohort of 114 MM patients. We identified one previously unreported gene locus associated with BiPN at 21q22.3 (rs2839629, PKNOX1; OR = 1.89, P= 6.47 x 10-7). PKNOX1 is known to regulate expression of MCP-1, a potent mediator of chemotherapy-induced peripheral neuropathy. rs2839629 is in strong linkage disequilibrium (LD, r2 = 0.87) with rs915854, localized 6.5kb centromeric to CBS encoding an endogenous H2S-producing enzyme. CBS-H2S signalling pathway is implicated in the pathogenesis of a variety of neurodegenerative and inflammatory disorders, and specifically in neuropathy models. Our data provide conclusive evidence for genetic susceptibility to BiPN in MM and new potential targets in neuro-protective strategies of treatment.
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| Overall design |
Identify risk variants for developing bortezomib-induced peripheral neuropathy (BiPN) within a cohort of 469 MM patients by means of genome wide association study, validation in an independent cohort of 114 MM patients
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| Contributor(s) |
Magrangeas F, Kuiper R, Avet-Loiseau H, Gouraud W, Guérin-Charbonnel C, Aussem A, Elghazel H, Suhard J, Der Sakissian H, Attal M, Sonneveld P, Dumontet C, Moreau P, van Duin M, Campion L, Minvielle S |
| Citation(s) |
27060151 |
| Submission date |
Feb 09, 2015 |
| Last update date |
Nov 27, 2018 |
| Contact name |
Wilfried Gouraud |
| Organization name |
ICO - UMGC
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| Department |
Integrated Center of Oncology René Gauducheau
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| Lab |
Omics Data Science Unit
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| Street address |
bd Jacques Monod
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| City |
Saint Herblain |
| ZIP/Postal code |
44805 |
| Country |
France |
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| Platforms (1) |
| GPL6801 |
[GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array |
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| Samples (469)
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| Relations |
| BioProject |
PRJNA275004 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE65777_RAW.tar |
13.9 Gb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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