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Promoter methylation is the most significant mechanism to regulate O 6 -methylguanine-DNA-methyltransferase ( MGMT ) expression. Single-nucleotide polymorphisms (SNPs) in the  MGMT  promoter region may also play a role. The aim of this study was to evaluate the clinical significance of SNPs in the  MGMT  promoter region of glioblastoma. Genomic DNAs from 118 glioblastomas were collected for polymerase chain reaction (PCR) amplification. Sanger sequencing was used to sequence the  MGMT  promoter region to detect SNPs. The results were correlated with  MGMT  status and patient survival. Rs1625649 was the only polymorphic SNP located at the  MGMT  promoter region in 37.5% of glioblastomas. Homozygous rs1625649 (AA genotype) was correlated with a higher  MGMT  methylation level and a lower protein expression, but the result was not statistically significant. In patients with  MGMT  methylated glioblastoma, cases with homozygous rs1625649 (AA genotype) were significantly associated with a lack of MGMT protein expression and a better progression-free survival (PFS) than the cases with wild type rs1625649 (CC genotype) or heterozygous rs1625649 (CA genotype). The survival impact was significant in multivariate analyses. In conclusion, the  MGMT  promoter homozygous rs1625649 (AA genotype) was found to correlate with a better PFS in patients with  MGMT  methylated glioblastoma.

The MGMT promoter single-nucleotide polymorphism rs1625649 had prognostic impact on patients with MGMT methylated glioblastoma