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Verfasst von:Campo, Chiara [VerfasserIn]   i
 Weinhold, Niels [VerfasserIn]   i
 Goldschmidt, Hartmut [VerfasserIn]   i
 Merz, Maximilian [VerfasserIn]   i
Titel:Bortezomib‐induced peripheral neuropathy
Titelzusatz:A genome‐wide association study on multiple myeloma patients
Verf.angabe:Campo Chiara, Silva Filho Miguel Inacio, Weinhold Niels, Mahmoudpour Seyed Hamidreza, Goldschmidt Hartmut, Hemminki Kari, Merz Maximilian, Försti Asta
E-Jahr:2017
Jahr:20 March 2017
Umfang:6 S.
Fussnoten:Gesehen am 12.04.2018
Titel Quelle:Enthalten in: Hematological oncology
Ort Quelle:New York, NY [u.a.] : Wiley Interscience, 1983
Jahr Quelle:2017
Band/Heft Quelle:36(2017), 1, Seite 232-237
ISSN Quelle:1099-1069
Abstract:Abstract The proteasome?inhibitor bortezomib was introduced into the treatment of multiple myeloma more than a decade ago. It is clinically beneficial, but peripheral neuropathy (PNP) is a side effect that may limit its use in some patients. To examine the possible genetic predisposing factors to PNP, we performed a genome?wide association study on 646 bortezomib?treated German multiple myeloma patients. Our aim was to identify genetic risk variants associated with the development of PNP as a serious side effect of the treatment. We identified 4 new promising loci for bortezomib?induced PNP at 4q34.3 (rs6552496), 5q14.1 (rs12521798), 16q23.3 (rs8060632), and 18q21.2 (rs17748074). Even though the results did not reach genome?wide significance level, they support the idea of previous studies, suggesting a genetic basis for neurotoxicity. The identified single nucleotide polymorphisms map to genes or next to genes involved in the development and function of the nervous system (CDH13, DCC, and TENM3). As possible functional clues, 2 of the variants, rs12521798 and rs17748074, affect enhancer histone marks in the brain. The rs12521798 may also impact expression of THBS4, which affects specific signal trasduction pathways in the nervous system. Further research is needed to clarify the mechanism of action of the identified single nucleotide polymorphisms in the development of drug?induced PNP and to functionally validate our in silico predictions.
DOI:doi:10.1002/hon.2391
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: http://dx.doi.org/10.1002/hon.2391
 Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/hon.2391
 DOI: https://doi.org/10.1002/hon.2391
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:bortezomib
 genetic variants
 GWAS
 multiple myeloma
 neuropathy
 SNPs
K10plus-PPN:1571944869
Verknüpfungen:→ Zeitschrift

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