Association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and susceptibility to Graves' ophthalmopathy

Mol Med Rep. 2016 Sep;14(3):2276-82. doi: 10.3892/mmr.2016.5458. Epub 2016 Jun 30.


The pathogenesis of Graves' ophthalmopathy (GO) remains to be entirely elucidated. The present study aimed to determine the association between phenotypic expression of the MTHFR gene and susceptibility to GO in patients with Graves' disease (GD). A prospective case‑controlled study was conducted with 122 patients with GD and GO (n=72) or without GO (n=50) and 100 healthy controls in South Korea. Patient history, including smoking, nutritional status, thyroid function and antithyroid antibodies were investigated and clinical activity score, VISA classification (which includes vision, inflammation, strabismus and appearance/exposure) and orbit computed tomography were evaluated. Fasting plasma total homocysteine (tHcy) concentration was measured, and genotype analysis of the MTHFR gene was conducted. The TT homozygous genotype was associated with a two‑fold increased risk of GO [adjusted odds ratio (AOR), 2.19; 95% confidence interval (CI), 0.78‑6.14]. However, this result was not significant. The TT genotype significantly increased the risk of GO compared with that in healthy controls (AOR, 2.92; 95% CI, 1.11‑7.65). The MTHFR 677CT/1298AA genotype decreased the risk of GO in patients with GD (AOR, 0.26; 95% CI, 0.08‑0.91). tHcy levels in patients with GD without GO were significantly higher than in patients with GO, however, they were within the normal limit. The current study identified an association between MTHFR polymorphisms and GO. These results will aid understanding of the pathogenesis of GO and facilitate development of genetic therapeutic strategies.

MeSH terms

  • Adult
  • Alleles
  • Biomarkers
  • Case-Control Studies
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genotype
  • Graves Ophthalmopathy / diagnosis
  • Graves Ophthalmopathy / genetics*
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Republic of Korea


  • Biomarkers
  • Methylenetetrahydrofolate Reductase (NADPH2)