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

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-methylenetetrahydrofol ate reductase (MTHFR), is linked with an increased incidence of thromboembo lic disease. Hyper-tHcy has been reported in patients with IBD. Aims-To assess the prevalence of the C677T MTHFR genotype and the contribut ion 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. Su bjects were categorised as homozygous for the thermolabile variant (TT), he terozygous for wild type and variant (CT), or homozygous for the wild type (CC). Results-Plasma homocysteine concentrations were significantly higher in pat ients with IBD than in healthy controls. A total of 17.5% of ulcerative col itis and 16.8% of Crohn's disease patients were homozygous for the C677T va riant compared with 7.3% of controls. Homozygosity (TT) for the variant was associated with higher plasma tHcy levels in patients with IBD and in heal thy controls. When all subjects who were TT for the variant were excluded, median plasma tHcy was still significantly higher in IBD than controls. Pla sma vitamin B-12 levels were lower in patients with IBD irrespective of MTH FR genotype. Conclusions-There is an association between the thermolabile MTHFR C677T va riant and IBD. This accounts in part for the raised plasma tHcy found in pa tients with IBD and may contribute to the increased incidence of thromboemb olic complications. All patients with IBD should receive low dose folic aci d and vitamin B-12 therapy to protect against the thromboembolic complicati ons of raised tHcy.