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Meta-analysis of associations between MTHFR and GST polymorphisms and susceptibility to multiple sclerosis

Young Ho Lee1, Young Ho Seo2, Jae-Hoon Kim2

  • 1Division of Rheumatology, Department of Internal Medicine, Korea University Medical Center, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, 136-705, Korea. lyhcgh@korea.ac.kr.

Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
|July 8, 2015
PubMed

Insights

This study found a link between the GSTT1 null genotype and multiple sclerosis (MS) susceptibility in Caucasian populations. However, no significant associations were observed for methylenetetrahydrofolate reductase (MTHFR) or other glutathione S-transferase (GST) gene polymorphisms with MS risk.

Area of Science:

  • Genetics
  • Neuroimmunology
  • Pharmacogenomics

Background:

  • Multiple sclerosis (MS) is a complex autoimmune disease affecting the central nervous system.
  • Genetic factors, including polymorphisms in folate metabolism and detoxification enzymes, are investigated for their role in MS susceptibility.
  • Methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase (GST) genes are key players in these pathways.

Purpose of the Study:

  • To investigate the association between specific polymorphisms in MTHFR and GST genes and the risk of developing multiple sclerosis.
  • To analyze the potential role of MTHFR C677T, A1298C, GSTP1 A313G, GSTM1 null, and GSTT1 null genotypes in MS susceptibility.

Main Methods:

  • A comprehensive meta-analysis was conducted, pooling data from 15 comparisons involving 2,486 MS patients and 2,861 controls.
  • Genotype data for MTHFR (C677T, A1298C), GSTP1 (A313G), GSTM1 (null), and GSTT1 (null) were analyzed.
  • Stratification by ethnicity, particularly Caucasian and Arab populations, was performed to identify population-specific associations.

Main Results:

  • No significant association was found between MS and MTHFR C677T or A1298C polymorphisms in the overall analysis or when stratified by ethnicity.
  • Similarly, no link was established between MS and GSTM1 null or GSTP1 A313G polymorphisms in Caucasian populations.
  • A significant association was observed between the GSTT1 null genotype and increased MS susceptibility specifically within Caucasian populations (OR = 1.945, p < 10⁻⁶).

Conclusions:

  • The GSTT1 null genotype is associated with an increased risk of multiple sclerosis in Caucasian individuals.
  • Polymorphisms in MTHFR (C677T, A1298C), GSTM1 (null), and GSTP1 (A313G) do not appear to be significantly associated with MS susceptibility across the studied populations.
  • Further research may elucidate the precise mechanisms underlying the GSTT1 null genotype's role in MS pathogenesis.
Keywords:
GSTsMTHFRMeta-analysisMultiple sclerosisPolymorphism

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