Single Nucleotide Polymorphism 309 Affects Murin-Double-Minute 2 Protein Expression But Not Glioma Tumorigenesis

Abstract

Murin-double-minute 2 (MDM2) is an important negative regulator of the p53 tumor suppressor, and affects the p53 protein level and transcriptional activity. The genotype of the single nucleotide polymorphism in the promoter region of MDM2 (single nucleotide polymorphism [SNP] 309) is associated with the MDM2 protein expression level and the onset age of several types of cancer. The SNP309 genotype was investigated in 254 Japanese patients with glioma and 50 healthy subjects. The genotype frequency of SNP309 was T/T homozygous in 62 patients (24%), T/G heterozygous in 126 (50%), and G/G homozygous in 66 (26%) of the glioma patients, and was similar in the healthy subjects. The G/G ratio was higher in our Japanese subjects than in Western populations. Immunohistochemical study of glioma tissues showed that the G/G genotype was associated with higher expression of MDM2 protein compared to the T/T genotype, suggesting that SNP309 attenuates MDM2 protein expression in vivo. However, no association was found between the SNP309 genotype and the histological grade of glioma, age at disease onset, or p53 gene mutation rate. In our study population, SNP309 affected MDM2 protein level, but had no significant involvement in glioma tumorigenesis.