Open Access

ARTICLE

A genetic variant study of bortezomib-induced peripheral neuropathy in Chinese multiple myeloma patients

YAN ZHANG, HEYANG ZHANG, JING WANG, XIN WEI, YI QU, FENG XU, LIJUN ZHANG^*

Department of Hematology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China

* Corresponding Author: LIJUN ZHANG. Email:

Oncology Research 2024, 32(5), 955-963. https://doi.org/10.32604/or.2023.043922

Received 16 July 2023; Accepted 05 December 2023; Issue published 23 April 2024

Abstract

Background: Bortezomib results in peripheral neuropathy (PN) in approximately 50% of patients, during multiple myeloma (MM) treatment, a complication known as Bortezomib-induced peripheral neuropathy (BIPN). The drug response varies among individuals. Genetic factor may play an important role in BIPN. Methods: A next-generation sequencing (NGS) panel containing 1659 targets from 233 genes was used to identify risk variants for developing BIPN in 204 MM patients who received bortezomib therapy. mRNA expression of MTHFR and ALDH1A1 in 62 peripheral blood samples was detected by real-time quantitative PCR (RT-qPCR). Serum homocysteine (Hcy) levels were detected in 40 samples by chemiluminescent microparticle immunoassay (CMIA). Results: Compared with the non-BIPN group (n = 89), a total of 8 significantly associated single nucleotide polymorphisms (SNPs) were identified in the BIPN group (n = 115): MTHFR (rs1801131, rs1801133, rs17421511), EPHX1 (rs1051740), MME (rs2016848), ALDH1A1 (rs6151031), HTR7 (rs1935349) and CYP2A6 (rs8192720). The mRNA expression level of MTHFR in newly diagnosed patients with peripheral neuritis after treatment (NP group) was lower than that of newly diagnosed patients without peripheral neuritis after treatment (NnP group) (1.70 ± 0.77 vs. 2.81 ± 0.97, p = 0.009). Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group (11.66 ± 1.79 μmol/L vs. 8.52 ± 3.29 μmol/L, p = 0.016) and healthy controls (11.66 ± 1.79 μmol/L vs. 8.55 ± 2.13 μmol/L, p ≤ 0.001). Conclusion: CYP2A6, EPHX1, MTHFR, ALDH1A1, HTR7, MME and BIPN are linked in Chinese MM patients. BIPN is more likely to occur in patients with lower MTHFR mRNA expression, which might result in higher serum Hcy levels.

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Supplementary Material

Supplementary Material File

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