Turkish Neurosurgery
Association of MTHFR, MTRR, and RAD54L Gene Variations with Meningioma and Their Correlation with the Tumor’s Histopathological Characteristics in Turkish Cohort
Timucin Avsar1, Rashid El-Mouyhiddin2, Seyma Calis4, Ozlem Yapicier6, Turker Kilic5
1Bahcesehir University, School of Medicine, Medical Biology Department, Istanbul,
2Bahcesehir University, Health Sciences Institute, Neuroscience Program, Istanbul,
3Bahcesehir University, School of Medicine, Neuroscience Laboratory, Istanbul,
4Istanbul Technical University, Graduate School of Science, Molecular Biology, Genetics and Biotechnology Graduate Program, Istanbul,
5Bahcesehir University, School of Medicine, Neurosurgery Department, Istanbul,
6Bahcesehir University, School of Medicine, Pathology Department, Istanbul,
DOI: 10.5137/1019-5149.JTN.33347-20.2

Aim:To elucidate the association of MTHFR, MTRR and RAD54L gene variations in Turkish meningioma cohort.Material and Methods:DNAs were isolated from 87 retrospective meningioma tumor samples. MTHFR, MTRR and RAD54L genes hot spot regions were amplified with specific primers by polymerase chain reaction (PCR) and next generation sequencing (NGS) was performed. All detected variations and single nucleotide polymorphisms were listed and compared with healthy control frequencies in different genomic databases. Histopathological characteristics of tumors and genomic variations were compared. The Pearson\'s chi-square test was used to detect statistical differences of SNPs and correlation analysis was performed.Results:rs1801131, rs1801133 and rs4846051 on MTHFR gene, rs1801394 on MTRR gene, rs1048771 on RAD54L gene frequencies found to be significantly altered in overall cohort of 87 meningioma patients. The frequency of rs18011031 is 0.09 in meningioma which is significantly correlated with WHO grades of tumors (p=0.038). The frequency of rs18011033 is 0.29, and significantly correlated with WHO grades of tumors (p=0.045). The frequency of rs4846051 is 0.18 in meningioma cohort which is significantly correlated with WHO grades of tumors (p=0.023) and also with low Ki67 proliferation index (p=0.00455). The frequency of rs1801394 is 0.15 and significantly associated with high Ki67 proliferation index on meningioma tumors (p=0.0144). The frequency of rs1048771 is 0.09 in meningioma cohort and it is significantly associated with non-necrotic histopathological form of tumor (p=0.05).Conclusion:We reported significant association between genetic alterations of folate metabolism (MTHFR, MTRR) and DNA repair mechanism (RAD54L) genes with the histopathological characteristics of the meningioma tumors. Five significant SNPs on these genes and four significant correlations of SNPs with histopathological characteristics were identified. Our study is a preliminary promising study to establish the genetics marker analysis for meningioma diagnosis and prognosis for folate metabolism and DNA repair associated genes in Turkish cohort.

Corresponding author : Timucin Avsar