Increased prevalence of methylenetetrahydrofolate reductase C677T variant in patients with inflammatory bowel disease, and its clinical implications

Gut. 1999 Sep;45(3):389-94. doi: 10.1136/gut.45.3.389.


Background: Inflammatory bowel disease (IBD) is associated with an increased incidence of thromboembolic disease. Hyperhomocysteinaemia (hyper-tHcy), a condition associated with the C677T variant of 5, 10-methylenetetrahydrofolate reductase (MTHFR), is linked with an increased incidence of thromboembolic disease. Hyper-tHcy has been reported in patients with IBD.

Aims: To assess the prevalence of the C677T MTHFR genotype and the contribution of this genotype to hyper-tHcy in patients with IBD.

Methods: Patients with established IBD (n=174) and healthy controls (n=273) were studied. DNA samples were genotyped for the MTHFR (C677T) mutation. Subjects were categorised as homozygous for the thermolabile variant (TT), heterozygous for wild type and variant (CT), or homozygous for the wild type (CC).

Results: Plasma homocysteine concentrations were significantly higher in patients with IBD than in healthy controls. A total of 17.5% of ulcerative colitis and 16.8% of Crohn's disease patients were homozygous for the C677T variant compared with 7.3% of controls. Homozygosity (TT) for the variant was associated with higher plasma tHcy levels in patients with IBD and in healthy controls. When all subjects who were TT for the variant were excluded, median plasma tHcy was still significantly higher in IBD than controls. Plasma vitamin B(12) levels were lower in patients with IBD irrespective of MTHFR genotype.

Conclusions: There is an association between the thermolabile MTHFR C677T variant and IBD. This accounts in part for the raised plasma tHcy found in patients with IBD and may contribute to the increased incidence of thromboembolic complications. All patients with IBD should receive low dose folic acid and vitamin B(12) therapy to protect against the thromboembolic complications of raised tHcy.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Erythrocytes / metabolism
  • Female
  • Folic Acid / blood
  • Folic Acid / therapeutic use
  • Genotype
  • Homocysteine / blood
  • Humans
  • Inflammatory Bowel Diseases / blood
  • Inflammatory Bowel Diseases / enzymology
  • Inflammatory Bowel Diseases / genetics*
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Middle Aged
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Point Mutation*
  • Prospective Studies
  • Vitamin B 12 / blood


  • Homocysteine
  • Folic Acid
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Vitamin B 12