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 and 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): (rs1801131, rs1801133, rs17421511), (rs1051740), (rs2016848), (rs6151031), (rs1935349) and (rs8192720). The mRNA expression level of 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 . 2.81 ± 0.97, = 0.009). Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group (11.66 ± 1.79 μmol/L . 8.52 ± 3.29 μmol/L, = 0.016) and healthy controls (11.66 ± 1.79 μmol/L . 8.55 ± 2.13 μmol/L, ≤ 0.001).

CONCLUSION

and BIPN are linked in Chinese MM patients. BIPN is more likely to occur in patients with lower mRNA expression, which might result in higher serum Hcy levels.