Abstract

Background: Methylenetetrahydrofolate reductase 677 (MTHFR 677) polymorphism may provoke hyperhomocysteinemia when folate status is low. The influence of MTHFR 677 mutation on homocysteine (HCY) levels in relation to vitamin B₁₂ and folate status was investigated in the current study. Subjects and methods: 113 vegetarians, 123 omnivorous Germans, and 117 omnivorous Syrians were recruited. MTHFR 677 genotype, HCY, methylmalonic acid (MMA), total serum vitamin B₁₂, serum folate, and vitamin B₆ were determined using conventional methods. Results: Omnivorous Germans displayed the lowest HCY levels compared with vegetarians and Syrians (median 8.0, 10.4, and 11.3 μmol/l, respectively). The highest serum folate and the highest MMA levels were found in vegetarians (median folate = 30.0; MMA = 355 nmol/l). Among vegetarians and Syrians, TT subjects had higher HCY levels than other genotypes which were, however, no longer significant in the highest folate tertiles. When the data were pooled, the odds ratio (OR, 95% CI) for HCY > 12 μmol/l was 3.81 (1.55–9.34) in TT compared with CC subjects. The OR increased to 28.85 (4.63–179.62) in TT subjects who had folate in the lowest tertile, and to 21.84 (4.81–99.1) in TT subjects who had MMA in the highest MMA tertile. Conclusion: MTHFR 677 TT individuals are more liable to hyperhomocysteinemia under vitamin B₁₂ deficiency than the other two genotypes. In such a case, relative folate shortage may progressively increase HCY levels. TT individuals may have increased folate and vitamin B₁₂ requirements compared to the other CC and CT genotypes.