Multiple sclerosis (MS) is the most common inflammatory and chronic disease of the central nervous system (CNS). A complex interaction between genetic, environmental, and epigenetic factors is involved in the pathogenesis of MS. With the advancement of GWAS, various variants associated with MS have been identified. This study aimed to evaluate the association of single-nucleotide polymorphisms (SNPs) rs4925166 and rs1979277 in the SHMT1, MAZ rs34286592, ERG rs2836425, and L3MBTL3 rs4364506 with MS. In this case-control study, the association of five SNPs in SHMT1, MAZ, ERG, and L3MBTL3 genes with relapsing-remitting MS (RR-MS) was investigated in 190 patients and 200 healthy individuals. Four SNPs including SHMT1 rs4925166, SHMT1 rs1979277, MAZ rs34286592, and L3MBTL3 rs4364506 were genotyped using PCR-RFLP and genotyping of ERG rs2836425 was performed by tetra-primer ARMS PCR. Our findings showed a significant difference in the allelic frequencies for the four SNPs of SHMT1 rs4925166, SHMT1 rs1979277, MAZ rs34286592, and ERG rs2836425, while there were no differences in the allele and genotype frequencies for L3MBTL3 rs4364506. These significant associations were observed for the following genotypes: TT and GG genotypes of SHMT1 rs4925166 (OR 0.47 and 1.90, respectively) genotype GG of SHMT1 rs1979277 (OR 0.63), genotype GG of MAZ rs34286592 (OR 0.61), TC and CC genotypes of ERG rs2836425 (OR 1.89 and 0.50, respectively). Our study highlighted that people who are carrying genotypes including GG (SHMT1 rs4925166) and TC (ERG rs2836425) have the highest susceptibility chance for MS, respectively. However, genotypes TT (SHMT1 rs4925166), CC (ERG rs2836425), GG (MAZ rs34286592), and GG (SHMT1 rs1979277) had the highest negative association (protective effect) with MS, respectively. L3MBTL3 rs4364506 was found neither as a predisposing nor a protective variant.
Keywords: Association study; ERG; L3MBTL3; MAZ; Multiple sclerosis; SHMT1; Single-nucleotide polymorphisms.