Introduction Hyperhomocysteinemia is a risk factor of cardiovascular disease. Homocysteine remethylation requires vitamin B₁₂, folate and methylenetetrahydrofolate reductase (MTHFR) enzyme. The common TT homozygosis of the C677T in the MTHFR gene is associated with reduced MTHFR activity. This study aims to assess the impact of serum levels of B₁₂ and folate on plasma homocysteine considering C677T polymorphism in a Brazilian sample.

Methods Serum vitamin B₁₂, folate, and homocysteine of 259 participants from a population-based survey in São Paulo, Brazil were used. The genotype for C677T was done with an allele-specific polymerase chain reaction. A generalised linear model with gamma distribution and link identity was applied to model homocysteine according to sex, age, vitamin B₁₂ as well as folate (cut-off at tercile 7.1 ng/ml) and C677T polymorphism (non-TT and TT) interaction.

Results Significant effects of males (p<0.01) and age (p<0.01) were found. An increase of 50 pg/ml in vitamin B₁₂ was associated with a reduction of 0.11 ng/ml in homocysteine levels (p=0.01). Finally, an interaction between polymorphism and folate was found (p<0.01), controlling all the covariates. A mean difference of 5.7 ng/ml of homocysteine levels was observed between below and above folate tercile among TT genotype (p<0.01) with a difference of only 1.1 ng/ml among non-TT (p<0.01). Homocysteine levels among participants with above tercile of folate were similar between non-TT and TT (p=0.57).

Conclusion Lower levels of folate are associated with higher levels of homocysteine, but in the presence of TT homozygote homocysteine is even higher.