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<br />folate metabolising enzymes have been reported to vary among different ethnic population. Here, we have studied the<br />association of SNPs of folate metabolizing genes with the primary brain tumors (glioma and meningioma) in North Indian<br />population. Methods: SNPs of genes coding for folate metabolizing enzymes was carried out in 288 study population<br />from North India [Glioma (n=108), Meningioma (n=76) and healthy-control (n=104)]. The allele-specific polymerase<br />chain reaction (ARMS-PCR) was used to analyse the SNP A1298C of the MTHFR (Methylenetetrahydrofolate-reductase)<br />and the SNP A66G of the methionine synthase reductase (MTRR) genes. The PCR-RLFP (Restriction Fragment Length<br />Polymorphism) was used to analyse the SNP C677T of the Methylene tetrahydrofolate-reductase and the SNP A2756G<br />of the methionine-synthase (MTR) genes. Serum homocysteine, vitamin B12 and folate levels were evaluated in controls/<br />patients serum using Chemiluminescence immunoassay and the levels were correlated with SNPs genotype. Results:<br />The CC genotype of MTHFR A1298C was observed to have reduced risk of having meningioma than AA genotype<br />(odd ratio=0.62, 95%CI 0.32-0.97, p=0.03). Similarly, the AG genotype of MTRR A66G showed reduced risk of<br />glioma than AA genotype (odd ratio=0.56, 95%CI 0.32-0.97, p=0.039). Furthermore, in patients with AA genotype of<br />MTR A2756G and CT genotype of MTHFR C677T showed higher serum homocysteine level than GG genotype (8.6<br />μmol/L, p=0.048) and CC genotype (11.2μmol/L, p=0.039) respectively. Conclusion: Our findings provide an insight<br />into the risk association of SNPs in MTHFR A1298C and MTRR A66G genes with glioma/meningioma patients.<br />Further studies are needed to evaluate their clinical implications.