Association of Single Nucleotide Polymorphisms (SNPs) in Genes Encoding for Folate Metabolising Enzymes with Glioma and Meningioma in Indian Population

Abstract

Background: The association of primary brain tumors with Single Nucleotide polymorphisms (SNPs) in genes of folate metabolising enzymes have been reported to vary among different ethnic population. Here, we have studied the association of SNPs of folate metabolizing genes with the primary brain tumors (glioma and meningioma) in North Indian population. Methods: SNPs of genes coding for folate metabolizing enzymes was carried out in 288 study population from North India [Glioma (n=108), Meningioma (n=76) and healthy-control (n=104)]. The allele-specific polymerase chain reaction (ARMS-PCR) was used to analyse the SNP A1298C of the MTHFR (Methylenetetrahydrofolate-reductase) and the SNP A66G of the methionine synthase reductase (MTRR) genes. The PCR-RLFP (Restriction Fragment Length Polymorphism) was used to analyse the SNP C677T of the Methylene tetrahydrofolate-reductase and the SNP A2756G of the methionine-synthase (MTR) genes. Serum homocysteine, vitamin B 12 and folate levels were evaluated in controls/patients serum using Chemiluminescence immunoassay and the levels were correlated with SNPs genotype. Results: The CC genotype of MTHFR A1298C was observed to have reduced risk of having meningioma than AA genotype (odd ratio=0.62, 95%CI 0.32-0.97, p=0.03). Similarly, the AG genotype of MTRR A66G showed reduced risk of glioma than AA genotype (odd ratio=0.56, 95%CI 0.32-0.97, p=0.039). Furthermore, in patients with AA genotype of MTR A2756G and CT genotype of MTHFR C677T showed higher serum homocysteine level than GG genotype (8.6 µmol/L, p=0.048) and CC genotype (11.2µmol/L, p=0.039) respectively. Conclusion: Our findings provide an insight into the risk association of SNPs in MTHFR A1298C and MTRR A66G genes with glioma/meningioma patients. Further studies are needed to evaluate their clinical implications.

MTHFR C677T and A1298C Polymorphisms in Breast Cancer, Gliomas and Gastric Cancer: A Review

“…Therefore, folate and vitamin B6 and B12 levels should be included in MTHFR polymorphism studies in cancer risk assessment. One literature report observed no significant difference in the serum folic acid and vitamin B12 levels concerning MTHFR polymorphisms [ 107 ]. Additionally, they found no association between meningioma or glioma risk and the MTHFR C677T polymorphism in the Indian population.…”

“…Several studies have found no association between polymorphisms and glioma development [ 100 , 107 , 111 ] and overall survival [ 112 ]. Notably, the influence of ethnicity in MTHFR polymorphisms is associated with glioma risk.…”

“…Conversely, a case-control study in Turkey with 74 patients and 94 controls demonstrated a higher frequency of the MTHFR 677TT genotype in high-grade gliomas than in the meningioma and control groups [ 115 ]. Brazilian and Turkish general populations have similar MTHFR 677TT polymorphism frequencies (7.7% and 7.1%, respectively), while the Indian population has a lower frequency (3.8–5%) [ 107 , 112 , 114 , 115 ]. These differences highlight the importance of studying diverse ethnic groups and stratifying glioma subtypes to perform more accurate analyses.…”

Role of MEK-ERK signaling mediated adhesion of glioma cells to extracellular matrix: Possible implication on migration and proliferation

“…Glioblastoma (GBM) represents the most common primary brain tumor in humans with an average incidence rate of 3.21 per 1,00,000 population [1]. Recent studies have reported the incidence of glioma in India is 1-4 per 1,00,000 [2][3][4]. The prognosis of GBM remains poor despite developments in neurosurgery and chemoradiotherapy.…”

<p>Association Between Genetic Polymorphisms In <em>TYMS </em>And Glioma Risk In Chinese Patients: A Case-Control Study</p>

“…It was reported that single-nucleotide polymorphisms (SNPs) were the most frequent single-nucleotide variations that occur in a specific position. Numerous SNPs, such as those in XRCC1/4, ERCC1/4, MGMT, PARP1, and MTHFR have been demonstrated to contribute to glioma susceptibility 1,7…”