Homocysteine plasma levels in patients treated with antiepileptic drugs depend on folate and vitamin B12 serum levels, but not on genetic variants of homocysteine metabolism.

BACKGROUND Antiepileptic drugs (AEDs) are commonly used in the treatment of epilepsy, psychiatric diseases and pain disorders. Several of these drugs influence blood levels of folate and vitamin B12 and, consequently, homocysteine. This may be relevant for AED effects and side effects. However, not only folate and vitamin B12, but also genetic variants modify homocysteine metabolism. Here, we aimed to determine whether there is a pharmacogenetic interaction between folate, vitamin B12 and genetic variants and homocysteine plasma level in AED-treated patients. METHODS In this mono-center study, we measured homocysteine, folate and vitamin B12 plasma levels in a population of 498 AED-treated adult patients with epilepsy. In addition, we analyzed the genotypes of seven common genetic variants of homocysteine metabolism: methylenetetrahydrofolate reductase (MTHFR) c.677C>T and c.1298A>C, methionine synthase (MTR) c.2756A>G, dihydrofolate reductase (DHFR) c.594+59del19bp, cystathionine β-synthase (CBS) c.844_855ins68, transcobalamin 2 (TC2) c.776C>G and methionine synthase reductase (MTRR) c.66G>A. RESULTS On multivariate logistic regression, folate and vitamin B12 levels, but none of the genetic variants, were predictive for homocysteine levels. CONCLUSIONS These data suggest that, in AED-treated patients, folate and vitamin B12 play important roles in the development of hyperhomocysteinemia, whereas genetic variants of homocysteine metabolism do not and thus do not contribute to the risk of developing hyperhomocysteinemia during AED treatment.