Genetic susceptibility to febrile seizures: case-control association studies.
OBJECTIVE
A genetic predisposition to febrile seizures (FS) has long been recognized. The inheritance appears to be polygenic in small families or sporadic cases of FS encountered in daily clinical practice. To determine whether candidate genes are responsible for the susceptibility to FS, we have performed genetic association studies in FS patients and controls.


METHODS
The single-nucleotide polymorphisms (SNPs) of genes involved in immune response (interleukin (IL) 1B), endocannabinoid signaling (CNR1), acid-base balance (SLC4A3, SLC9A1, SLC9A3), gap junction channel (CX43), and GABA(A) receptor trafficking (PRIP1) were examined in 249 FS patients (186 simple and 63 complex FS) and 225 controls.


RESULTS
There were no significant differences in the allele frequencies of the SNPs between controls and all FS, simple FS, and complex FS patients. When the simple FS patients were divided into two groups according to either having (familial) or not having a family history of FS in close relatives (sporadic), there was a significant association between IL1B -511 SNP and sporadic simple FS (p=0.003).


CONCLUSIONS
These data suggest that cytokine genes may act as enhancers or attenuators of FS susceptibility. Genetic association study may be an effective approach to understanding the molecular basis of FS at least in a subgroup of patients.
Kira
Ryutaro
R
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. kirari@pediatr.med.kyushu-u.ac.jp
Ishizaki
Yoshito
Y
Torisu
Hiroyuki
H
Sanefuji
Masafumi
M
Takemoto
Megumi
M
Sakamoto
Kanji
K
Matsumoto
Shigetaka
S
Yamaguchi
Yui
Y
Yukaya
Naoko
N
Sakai
Yasunari
Y
Gondo
Kenjiro
K
Hara
Toshiro
T
D016022:Case-Control Studies; D002648:Child; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D003294:Seizures, Febrile / Q000235:genetics*; D017422:Sequence Analysis, DNA
C508585:IL1B protein, human; D053583:Interleukin-1beta