TY  - EJOU
AU  - ZHANG, YAN 
AU  - ZHANG, HEYANG 
AU  - WANG, JING 
AU  - WEI, XIN 
AU  - QU, YI 
AU  - XU, FENG 
AU  - ZHANG, LIJUN 

TI  - A genetic variant study of bortezomib-induced peripheral neuropathy in Chinese multiple myeloma patients
T2  - Oncology Research

PY  - 2024
VL  - 32
IS  - 5
SN  - 1555-3906

AB  -  <b>Background:</b> 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. <b>Methods:</b> 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 <i>MTHFR</i> and <i>ALDH1A1</i> 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). <b>Results:</b> 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): <i>MTHFR</i> (rs1801131, rs1801133, rs17421511), <i>EPHX1</i> (rs1051740), <i>MME</i> (rs2016848), <i>ALDH1A1</i> (rs6151031), <i>HTR7</i> (rs1935349) and <i>CYP2A6</i> (rs8192720). The mRNA expression level of <i>MTHFR</i> 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 <i>vs</i>. 2.81 ± 0.97, <b><i>p</i> </b>= 0.009). Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group (11.66 ± 1.79 μmol/L <i>vs</i>. 8.52 ± 3.29 μmol/L, <b><i>p</i> </b>= 0.016) and healthy controls (11.66 ± 1.79 μmol/L <i>vs</i>. 8.55 ± 2.13 μmol/L, <b><i>p</i> </b>≤ 0.001). <b>Conclusion:</b> <i>CYP2A6, EPHX1, MTHFR, ALDH1A1, HTR7, MME</i> and BIPN are linked in Chinese MM patients. BIPN is more likely to occur in patients with lower <i>MTHFR</i> mRNA expression, which might result in higher serum Hcy levels.
KW  - Multiple Myeloma; Peripheral neuropathy; Bortezomib; Bortezomib-induced peripheral neuropathy; Next-generation sequencing; <i>MTHFR</i>; Serum Hcy

DO  - 10.32604/or.2023.043922