Objective To investigate the relationship between Lin-12-like(C.elegans)(SEL1L)suppressant gene polymorphism and overall survival or temozolomide(TMZ)sensitivity in patients with glioma.Methods A total of 66 patients with pathologically confirmed glioma,in-cluding 32 cases of glioblastoma(GBM)and 34 cases of low-grade glioma(LGG),were enrolled between January 2019 and January 2023.All patients received TMZ adjuvant chemotherapy and/or radiotherapy after surgery.Tumor tissue O-6-methylguanine-DNA methyltransferase(MGMT)promoter methylation was measured by bisulfite transformation and pyrosequencing,and the frequency of rs12435998 single nucleotide genetic variation in SEL1L intron 3 in tumor tissue and peripheral blood mononuclear cells(control samples)was determined by SNaPShotTM assays.Overall survival(OST)was followed up.Results The allele frequency of rs12435998 mi-nor allele G was 19.70%(26/132)in tumor samples,but only 9.85%(13/132)in control sam-ples.The proportion of AG/GG genotypes in GBM patients was significantly higher(P=0.047).In addition,the rs12435998 genotype in tumor tissue matched the rs12435998 genotype trend in control sample.Tumor rs12435998 genotype was not associated with OST in patients with GBM(P=0.520)or MGMT hypermethylation(P=0.299).However,LGG patients with rs12435998AG/GG genotype had a shorter median OST(17.10 months vs.53.20 months)(HR:6.844;95%CI:1.991~23.530;P=0.002).Similarly,for MGMT hypomethylation patients,the median OST in patients with tumor rs12435998AG/GG genotype was shorter than that in patients with AA genotype(7.10 months vs.44.80 months)(HR:2.937;95%CI:1.155~7.464;P=0.024).Conclusion SEL1L rs12435998 gene polymorphism may be a new molecular stratification of LGG,and its G suballele is associated with poor TMZ sensitivity and survival prognosis.