The role of CYP2C9 polymorphisms in phenytoin-related cerebellar atrophy

Abstract

PurposePhenytoin is known to be able to induce cerebellar atrophy in patients with epilepsy. It is also known that a CYP2C9 mutation (*2 or *3) reduces phenytoin metabolism by 25–50% and can increase the risk of phenytoin-related side effects. We examined the influence of CYP2C9 polymorphisms on total cerebellar volume and cerebellar gray and white matter volumes in patients with epilepsy taking phenytoin. MethodsFor the genotyping, 100 adult patients with documented epilepsy who had been taking phenytoin for >1 year were selected. From this group, we randomly selected 19 mutant individuals (MT group; CYP2C9*2 and *3) for a whole-brain volume measurement using MRI and 19 wild-type individuals (group WT; CYP2C9*1) with similar clinical and demographic characteristics to those in the MT group for comparison. Total intracranial volume measurements were used to normalize the acquired volumes, which were separated into gray matter volume, white matter volume, and total volume. ResultsThe MT group exhibited a significant reduction in cerebellar white matter volume (p=0.002) but not in total cerebellar volume. ConclusionOur study is the first to report evidence linking CYP2C9 polymorphism and a reduction in cerebellar volume in epileptic users of phenytoin.