Document Detail


The role of CYP2C9 polymorphisms in phenytoin-related cerebellar atrophy.
MedLine Citation:
PMID:  23298603     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: 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.
CONCLUSION: Our study is the first to report evidence linking CYP2C9 polymorphism and a reduction in cerebellar volume in epileptic users of phenytoin.
Authors:
Carlos A Twardowschy; Lineu C Werneck; Rosana H Scola; João G Borgio; Luciano De Paola; Carlos Silvado
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-06
Journal Detail:
Title:  Seizure     Volume:  22     ISSN:  1532-2688     ISO Abbreviation:  Seizure     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-11     Completed Date:  2013-08-26     Revised Date:  2014-10-21    
Medline Journal Info:
Nlm Unique ID:  9306979     Medline TA:  Seizure     Country:  England    
Other Details:
Languages:  eng     Pagination:  194-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Alleles
Anticonvulsants / adverse effects*,  therapeutic use
Aryl Hydrocarbon Hydroxylases / genetics*
Atrophy / chemically induced,  genetics*
Cerebellar Diseases / chemically induced,  genetics*
Epilepsy / drug therapy,  genetics*
Female
Gene-Environment Interaction
Genotype
Humans
Male
Middle Aged
Phenytoin / adverse effects*,  therapeutic use
Polymorphism, Single Nucleotide*
Chemical
Reg. No./Substance:
0/Anticonvulsants; 6158TKW0C5/Phenytoin; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/CYP2C9 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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