MTHFR and Seizure Risk

The MTHFR gene provides instructions for making an enzyme called methylenetetrahydrofolate reductase. This enzyme is important for a chemical reaction involving the vitamin folate (also called vitamin B9). Specifically, this enzyme converts a form of folate called 5,10-methylenetetrahydrofolate to a different form of folate called 5-methyltetrahydrofolate. This is the primary form of folate found in blood.

Polymorphisms in the MTHFR gene can alter or decrease the activity of methylenetetrahydrofolate reductase, leading to a mild increase of homocysteine in the blood (hyperhomocysteinemia). The two MTHFR gene polymorphisms that are the most common and the most frequently studied are 677C>T and a change that replaces the nucleotide adenosine with the nucleotide cytosine at position 1298 (written as 1298A>C).

The well-studied C677T variant in the methylenetetrahydrofolate reductase (MTHFR) enzyme is a biologically plausible genetic risk factor for seizures or epilepsy. First, plasma levels of homocysteine, a pro-convulsant, are moderately elevated in individuals with the homozygote TT genotype. Furthermore, the TT genotype has been previously linked with migraine with aura and with alcohol withdrawal seizures. Finally, several small studies have suggested that the TT genotype may be overrepresented in epilepsy patients.1

Related to:
Epilepsy, C677T variant