Genetic and nutritional predictors of hyperhomocysteinemia in inflammatory bowel disease.

Abstract

TO THE EDITOR: We read with interest the article by Romagnuolo et al. (1) regarding the prevalence and the predictors of hyperhomocysteinemia in patients with inflammatory bowel disease (IBD). The authors concluded that hyperhomocysteinemia is significantly more common in IBD patients than in healthy controls (15.4% vs 2.2%, p < 0.05), as previously reported (2, 3, 4), and that advanced age, male sex, vitamin B12 deficiency or lower vitamin B12 serum levels, and multivitamin therapy were independently associated with hyperhomocysteinemia (1). Several studies showed that vitamin deficiencies (both folic acid and vitamin B12) are the major determinants of hyperhomocysteinemia in IBD patients (2, 3, 4). However, increased plasma homocysteine levels are typically caused not only by nutritional deficiencies in vitamin cofactors such as folic acid, vitamin B12, and vitamin B6, but also by genetic defects in the enzymes involved in homocysteine metabolism. The most common enzyme defect associated with moderately raised homocysteine is a point mutation (C to T substitution at nucleotide 677) in the coding region of the gene for methylenetetrahydrofolate reductase (MTHFR), which is involved in the remethylation pathway of homocysteine. Recently, we performed a study in a population of 64 IBD patients in whom vitamin B12 and folic acid levels were determined together with the prevalence of the MTHFR genotypes. Among the 11 IBD patients carrying the TT MTHFR genotype, six had hyperhomocysteinemia, of whom five had concurrent folate and/or vitamin B12 deficiency. The relative risk of developing hyperhomocysteinemia was 5.3-fold (95% CI = 2.9–9.6) in IBD patients with the TT MTHFR genotype associated with folate and/or vitamin B12 deficiency, in comparison to individuals with CC or CT MTHFR genotypes and adequate levels of folate and/or vitamin B12. Furthermore, in patients' homozygotic for the C677T MTHFR gene mutation there is an increased folate requirement to mantain plasma homocysteine within normal levels (5). Thus, the IBD patients with this genetic background are at increased risk to develop hyperhomocysteinemia and may need vitamin B12 and folate supplementation. In conclusion, we suggest that determination of both the MTHFR genotype and vitamin status may predict the risk of developing hyperhomocysteinemia in IBD patients.