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 B12 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.

Keywords: SNP; MTHFR/MTRR/MTR; glioma/meningioma; Indian population; homocysteine; folate; Vitamin B12.

Figure 1

Overview of Folate and Homocysteine metabolism in human. Schematic description of one-carbon metabolism pathways of folate cycle showing Folate and Homocysteine metabolism. MTHFR (Methylene tetrahydrofolate reductase), MTR (methionine synthase), MTRR (Methyl tetrahydrofolate Homocysteine Methyl Transferase Reductase) enzymes, MAT (Methionine Adenosyl Transferase), MT (methyltransferase), SAHH (S-adenosylhomocysteine hydrolase), CBS (Cystathionine beta-synthase) and CTH (cystathionine γ-lyase enzyme).