Document Detail

Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility.
MedLine Citation:
PMID:  15120748     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Our research program uses genetic linkage and association analysis to identify human seizure sensitivity and resistance alleles. Quantitative trait loci mapping in mice led to identification of genetic variation in the potassium ion channel gene Kcnj10, implicating it as a putative seizure susceptibility gene. The purpose of this work was to translate these animal model data to a human genetic association study. METHODS: We used single stranded conformation polymorphism (SSCP) electrophoresis, DNA sequencing and database searching (NCBI) to identify variation in the human KCNJ10 gene. Restriction fragment length polymorphism (RFLP) analysis, SSCP and Pyrosequencing were used to genotype a single nucleotide polymorphism (SNP, dbSNP rs#1130183) in KCNJ10 in epilepsy patients (n = 407) and unrelated controls (n = 284). The epilepsy group was comprised of patients with refractory mesial temporal lobe epilepsy (n = 153), childhood absence (n = 84), juvenile myoclonic (n = 111) and idiopathic generalized epilepsy not otherwise specified (IGE-NOS, n = 59) and all were of European ancestry. RESULTS: SNP rs#1130183 (C > T) alters amino acid 271 (of 379) from an arginine to a cysteine (R271C). The C allele (Arg) is common with conversion to the T allele (Cys) occurring twice as often in controls compared to epilepsy patients. Contingency analysis documented a statistically significant association between seizure resistance and allele frequency, Mantel-Haenszel chi square = 5.65, d.f. = 1, P = 0.017, odds ratio 0.52, 95% CI 0.33-0.82. CONCLUSION: The T allele of SNP rs#1130183 is associated with seizure resistance when common forms of focal and generalized epilepsy are analyzed as a group. These data suggest that this missense variation in KCNJ10 (or a nearby variation) is related to general seizure susceptibility in humans.
R J Buono; F W Lohoff; T Sander; M R Sperling; M J O'Connor; D J Dlugos; S G Ryan; G T Golden; H Zhao; T M Scattergood; W H Berrettini; T N Ferraro
Related Documents :
20630778 - Milder phenotype with scn1a truncation mutation other than smei.
11979448 - Genetic analysis of ret, gfr alpha 1 and gdnf genes in spanish families with multiple e...
14598228 - Mutation analysis of the leucine-rich, glioma inactivated 1 gene (lgi1) in japanese feb...
8901418 - Ret mutations in human disease.
21296128 - Genetic and environmental influences onstructural variability of the brain in pediatric...
12354768 - A novel mutation (t65p) in the pas domain of the human potassium channel herg results i...
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Epilepsy research     Volume:  58     ISSN:  0920-1211     ISO Abbreviation:  Epilepsy Res.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-05-03     Completed Date:  2004-07-06     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8703089     Medline TA:  Epilepsy Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  175-83     Citation Subset:  IM    
Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, 415 Curie Boulevard, CRB-120, Philadelphia, PA 19104-6140, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Chi-Square Distribution
Confidence Intervals
Gene Frequency / genetics
Genetic Predisposition to Disease / genetics*
Genetic Variation / genetics*
Odds Ratio
Potassium Channels / genetics*
Potassium Channels, Inwardly Rectifying*
Quantitative Trait Loci / genetics
Seizures / genetics*
Grant Support
Reg. No./Substance:
0/Potassium Channels; 0/Potassium Channels, Inwardly Rectifying; 0/potassium inwardly-rectifying channel, subfamily J, member 10

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

Previous Document:  Anticonvulsant effects of levetiracetam and levetiracetam-diazepam combinations in experimental stat...
Next Document:  Influence of sympathetic autonomic arousal on cortical arousal: implications for a therapeutic behav...