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Genetic factors influencing the risk of multiple myeloma bone disease

A major complication of multiple myeloma (MM) is the development of osteolytic lesions, fractures and bone pain. To identify genetic variants influencing the development of MM bone disease (MBD), we analyzed MM patients of European ancestry (totaling 3774), which had been radiologically surveyed for...

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Bibliographische Detailangaben
Hauptverfasser: Johnson, David C. (VerfasserIn) , Weinhold, Niels (VerfasserIn) , Chen, Bowang (VerfasserIn) , Försti, Asta (VerfasserIn) , Nickel, Jolanta (VerfasserIn) , Hillengaß, Jens (VerfasserIn) , Bertsch, Uta (VerfasserIn) , Goldschmidt, Hartmut (VerfasserIn)
Weitere Verfasser: Hemminki, Kari (BerichterstatterIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 12 January 2016
In: Leukemia
Year: 2016, Jahrgang: 30, Heft: 4, Pages: 883-888
ISSN:1476-5551
DOI:10.1038/leu.2015.342
Online-Zugang:Verlag, Volltext: https://doi.org/10.1038/leu.2015.342
Verlag, Volltext: https://www.nature.com/articles/leu2015342
Volltext
Verfasserangaben:DC Johnson, N Weinhold, J Mitchell, B Chen, OW Stephens, A Försti, J Nickel, M Kaiser, WA Gregory, D Cairns, GH Jackson, P Hoffmann, MM Noethen, J Hillengass, U Bertsch, B Barlogie, FE Davis, K Hemminki, H Goldschmidt, RS Houlston and GJ Morgan
Beschreibung
Zusammenfassung:A major complication of multiple myeloma (MM) is the development of osteolytic lesions, fractures and bone pain. To identify genetic variants influencing the development of MM bone disease (MBD), we analyzed MM patients of European ancestry (totaling 3774), which had been radiologically surveyed for MBD. Each patient had been genotyped for ~6 00 000 single-nucleotide polymorphisms with genotypes for six million common variants imputed using 1000 Genomes Project and UK10K as reference. We identified a locus at 8q24.12 for MBD (rs4407910, OPG/TNFRSF11B, odds ratio=1.38, P=4.09 × 10-9) and a promising association at 19q13.43 (rs74676832, odds ratio=1.97, P=9.33 × 10-7). Our findings demonstrate that germline variation influences MBD and highlights the importance of RANK/RANKL/OPG pathway in MBD development. These findings will contribute to the development of future strategies for prevention of MBD in the early precancerous phases of MM.
Beschreibung:Gesehen am 10.06.2020
Beschreibung:Online Resource
ISSN:1476-5551
DOI:10.1038/leu.2015.342

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