title: The role of CYP2C9 polymorphisms in phenytoin-related cerebellar atrophy.
abstract: OBJECTIVE
  Phenytoin 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.
  
  
  METHODS
  For 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.
  
  
  RESULTS
  The MT group exhibited a significant reduction in cerebellar white matter volume (p=0.002) but not in total cerebellar volume.
  
  
  CONCLUSIONS
  Our study is the first to report evidence linking CYP2C9 polymorphism and a reduction in cerebellar volume in epileptic users of phenytoin.
authors.affiliation: Neurology Service and Molecular Biology Laboratory, Hospital de Clínicas, Universidade Federal do Paraná, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Twardowschy
authors.forename: Lineu C
authors.initials: LC
authors.lastname: Werneck
authors.forename: Rosana H
authors.initials: RH
authors.lastname: Scola
authors.forename: João G
authors.initials: JG
authors.lastname: Borgio
authors.forename: Luciano
authors.initials: L
authors.lastname: De Paola
authors.forename: Carlos
authors.initials: C
authors.lastname: Silvado
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001284:Atrophy / Q000139:chemically induced / Q000235:genetics*; D002526:Cerebellar Diseases / Q000139:chemically induced / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000009:adverse effects* / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide
chemical_list: D000927:Anticonvulsants; D010672:Phenytoin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases