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

作　　者：YAN ZHANG HEYANG ZHANG JING WANG XIN WEI YI QU FENG XU LIJUN ZHANG 

机构地区：[1]Department of Hematology,The First Affiliated Hospital of China Medical University,Shenyang,110001,China

出　　处：《Oncology Research》2024年第5期955-963,共9页肿瘤学研究（英文）

基　　金：supported by the“GZ Hematologic Malignancy MARKER GHROMOS of Education Department of Liaoning Province”Grant(Grant Number:07102).

摘　　要：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 nextgeneration 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±1.79μmol/L vs.8.52±3.29μmol/L,p=0.016)and healthy controls(11.66±1.79μmol/L vs.8.55±2.13μmol/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.

关 键 词：Multiple Myeloma Peripheral neuropathy BORTEZOMIB Bortezomib-induced peripheral neuropathy Next-generation sequencing MTHFR Serum Hcy 

分 类 号：R733.3[医药卫生—肿瘤]