The role of hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) C677T mutation in patients with retinal artery occlusion

Am J Ophthalmol. 2002 Jul;134(1):57-61. doi: 10.1016/s0002-9394(02)01471-x.


Purpose: Hyperhomocysteinemia has been established as an important risk factor for cardiovascular diseases. The aim of the present study was to investigate whether hyperhomocysteinemia and/or homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation are associated with an increased risk for retinal artery occlusion (RAO).

Design: Retrospective case-control study.

Methods: We studied 105 consecutive patients with retinal artery occlusion and 105 age and sex-matched control subjects. Fasting plasma homocysteine levels were determined by high-performance liquid chromatography, while genotypes of the MTHFR C677T mutation were determined by polymerase chain reaction.

Results: Mean plasma homocysteine levels were significantly higher in patients with RAO compared with control subjects (12.2 +/- 4.8 micromol/l vs 10.3 +/- 3.4 micromol/l; P =.003). Hyperhomocysteinemia was defined by the 95th percentile of control plasma homocysteine levels as 15.8 micromol/l. Twenty (19.1%) patients with RAO exceeded this level and were therefore classified as hyperhomocysteinemic compared with 5 (4.8%) control subjects (P =.003). The odds ratio for these patients was calculated at 4.7 (95% confidence interval [CI], 1.5-15.1). Mean plasma folate levels were significantly lower in patients than in the control group (5.6 +/- 2.3 ng/ml vs. 6.3 +/- 2.5 ng/ml; P =.04). The prevalence of the homozygous genotype of methylenetetrahydrofolate reductase C677T mutation did not significantly differ between patients and controls.

Conclusions: Our results suggest that hyperhomocysteinemia, but not homozygosity, for the MTHFR C677T mutation is associated with RAO.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Chromatography, High Pressure Liquid
  • DNA / analysis
  • Female
  • Genotype
  • Homocysteine / blood
  • Humans
  • Hyperhomocysteinemia / blood
  • Hyperhomocysteinemia / complications*
  • Hyperhomocysteinemia / genetics
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Middle Aged
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Point Mutation*
  • Polymerase Chain Reaction
  • Retinal Artery Occlusion / blood
  • Retinal Artery Occlusion / etiology*
  • Retinal Artery Occlusion / genetics
  • Retrospective Studies
  • Risk Factors


  • Homocysteine
  • DNA
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)