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Association of SHMT1, MAZ, ERG, and L3MBTL3 Gene Polymorphisms with Susceptibility to Multiple Sclerosis

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Abstract

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.

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Acknowledgement

We would like to thank the patient and healthy controls for providing us with the complementary information. This research has received a grant neither from any funding agency in the public, nor from the commercial/profit sectors.

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  1. Seyede Zahra Nazari Mehrabani and Mohammad Hossein Shushizadeh contributed to the work equally.

Authors and Affiliations

  1. Department of Molecular Genetics, Islamic Azad University, East Tehran branch, Tehran, Iran

    Seyede Zahra Nazari Mehrabani

  2. Doctor of Clinical Lab Science, Pasteur Medical Lab Shush Danial Iran, Dezful Medical University, Dezful, Iran

    Mohammad Hossein Shushizadeh

  3. Department of Genetics, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran

    Mohammad Foad Abazari & Maryam Nouri Aleagha

  4. Department of Biology, Faculty of Sciences, Arak University, Arak, Iran

    Abbas Ardalan

  5. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Rasoul Abdollahzadeh & Asaad Azarnezhad

  6. Cellular and Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Asaad Azarnezhad

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  1. Seyede Zahra Nazari Mehrabani
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Correspondence to Rasoul Abdollahzadeh or Asaad Azarnezhad.

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Nazari Mehrabani, S.Z., Shushizadeh, M.H., Abazari, M.F. et al. Association of SHMT1, MAZ, ERG, and L3MBTL3 Gene Polymorphisms with Susceptibility to Multiple Sclerosis. Biochem Genet 57, 355–370 (2019). https://doi.org/10.1007/s10528-018-9894-1

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