Genetic variation in Charcot-Marie-Tooth genes contributes to sensitivity to paclitaxel-induced peripheral neuropathy

Yongzhen Chen, Fang Fang, Kelley M. Kidwell, Kiran Vangipuram, Lauren A. Marcath, Christina L. Gersch, James M. Rae, Daniel F. Hayes, Ellen M. Lavoie Smith, N. Lynn Henry, Andreas S. Beutler, Daniel L. Hertz

Research output: Contribution to journalArticle

Abstract

Aim: This study explored whether inherited variants in genes causing the hereditary neuropathy condition Charcot-Marie-Tooth disease are associated with sensitivity to paclitaxel-induced peripheral neuropathy (PN). Patients & methods: Hereditary neuropathy genes previously associated with risk of paclitaxel-induced PN were sequenced in paclitaxel-treated patients. Eight putative genetic predictors in five hereditary neuropathy genes (ARHGEF10, SBF2, FGD4, FZD3 and NXN) were tested for association with PN sensitivity after accounting for systemic exposure and clinical variables. Results: FZD3 rs7833751, a proxy for rs7001034, decreased PN sensitivity (additive model, β = -0.41; 95#x00025; CI: -0.66 to -0.17; p = 0.0011). None of the other genetic predictors were associated with PN sensitivity. Conclusion: Our results support prior evidence that FZD3 rs7001034 is protective of PN and may be useful for individualizing paclitaxel treatment to prevent PN.

Original languageEnglish (US)
Pages (from-to)841-851
Number of pages11
JournalPharmacogenomics
Volume21
Issue number12
DOIs
StatePublished - Aug 2020

Keywords

  • ARHGEF10
  • FZD3
  • paclitaxel
  • peripheral neuropathy
  • pharmacogenomics

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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    Chen, Y., Fang, F., Kidwell, K. M., Vangipuram, K., Marcath, L. A., Gersch, C. L., Rae, J. M., Hayes, D. F., Lavoie Smith, E. M., Henry, N. L., Beutler, A. S., & Hertz, D. L. (2020). Genetic variation in Charcot-Marie-Tooth genes contributes to sensitivity to paclitaxel-induced peripheral neuropathy. Pharmacogenomics, 21(12), 841-851. https://doi.org/10.2217/pgs-2020-0053