Association Of MGMT Gene Promoter Methylation And Expression In Gliomas And Its Relationship With SNP

Glioma is the most common primary brain tumors of adult. Clinical studies have shown that the expression level and methylation degree of O6-methylguanine-DNA methyltransferese correlated with the living time of glioma patients receiving temozolomide.There is significant relationship between expression of MGMT gene and genotype of SNP and methylation of CpG sites of the MGMT promoter regions. Methylation of MGMT promoter was reported to be an independent prognostic and predictive factor in glioma patients who received temozolomide treatment. Ninety-eight CpG sites of MGMT promoter exist a considerable heterogeneity. Clinical detection of MGMT gene only focus within 10 CpG sites, there still exist many questions about these sites.60 samples of glioma patients of Chinese were collected, and genotype of seven SNPs were detected by direct sequencing, methylation status of ninety-eight CpG sites were completed test by pyrosequencing, and expression levels of glioma samples were detected by real-time quantitative PCR. The purpose is to find the SNP loci and CpG sites that were most closely associated with expression of MGMT gene.In this study, we found TT genotype of rs11016798 was correlated with low expression of MGMT gene. Significant difference for methylation of MGMT gene was found in glioma patients. The group of hypermethylation included 14 patients with considerable methylation at almost all of the CpG sites tested (average,37.4%), The group of hypomethylation included the 28 other patients that had a lower global methylation level (average,12.9%). In addition, there was close correlation between MGMT gene expression and methylation. Further study, we found 38 CpG sites, whose hypermethylation is significant inhibition gene expression of MGMT(p< 0.0001). These CpG sites covered four areas: -436 to -374, -342 to -249, -228 to-172,95 to 153. At the same time, the research showed that mutations of IDH1 and hypermethylation of MGMTwere significantly correlated.In summary, from the study of MGMT gene in Glioma, some SNP loci and CpG sites closely associated with gene expression were found, which would provides the basis for individualized chemotherapy in Chinese glioma patients.