Mgmt Gene Rs1625649 Polymorphism in Iranian Patients With Brain Glioblastoma: A Case Control Study Publisher



Safaei R¹ ; Mojtahedi H^{2, 3} ; Hanaei S⁴ ; Razavi A⁵ ; Esmaeili M⁵ ; Sadr M² ; Rezaei A⁵ ; Edalatfar M⁶ ; Kashani HK⁶ ; Sadeghinaini M⁷ ; Darbeheshti F⁸ ; Gharehdaghi J⁹ ; Forouzesh M⁹ ; Ebrahimi A¹⁰ Show All Authors Show Affiliations
Source: Avicenna Journal of Medical Biotechnology Published:2023

Abstract

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor with poor prognosis and high potential of dispersion to other brain tissues in adult. Effective and modern choices of treatment including chemotherapy with alkylating agents marginally extend survival of GBM. However, alkylating agents can lead to highly harmful mismatch during DNA replication causing apoptosis and cell death. Accordingly, O6-Methylguanine-DNA methyltransferase (MGMT) removes alkyl adducts, thereby causing resistance to alkylating drugs. Single-Nucleotide Polymorphisms (SNPs) in MGMT promoter region may play a role in the regulation of MGMT expression and prediction of glioma development risk. In order to evaluate the clinical significance of rs1625649 SNP in the MGMT promoter region of glioblastoma, genomic DNA from a series of 54 patients with GBM and 50 healthy individuals in Iranian population were collected for tetra ARMS PCR amplification. None of the A or C alleles were associated with tumor occurrence, the AA genotype was more frequent in healthy subjects, and the AC genotype was 4.6 times more common in patients with GBM. The longest survival time was observed in the CC genotype; however, this difference was not statistically significant. On the other hand, homozygous rs1625649 (AA genotype) was significantly associated with a better survival than the cases with heterozygous rs1625649 (CA genotype) or wild type rs1625649 (CC genotype), predicting better response to temozolomide-based chemotherapy. © 2023, Avicenna Journal of Medical Biotechnology. All rights reserved.