Kira Ryutaro, Ishizaki Yoshito, Torisu Hiroyuki, Sanefuji Masafumi, Takemoto Megumi, Sakamoto Kanji, Matsumoto Shigetaka, Yamaguchi Yui, Yukaya Naoko, Sakai Yasunari, Gondo Kenjiro, Hara Toshiro
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Brain Dev. 2010 Jan;32(1):57-63. doi: 10.1016/j.braindev.2009.09.018. Epub 2009 Oct 23.
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.
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.
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).
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.
热性惊厥（FS）的遗传易感性早已得到认可。在日常临床实践中遇到的FS小家族或散发病例中，其遗传方式似乎是多基因的。为了确定候选基因是否与FS易感性有关，我们对FS患者和对照进行了基因关联研究。
在249例FS患者（186例单纯性FS和63例复杂性FS）和225例对照中，检测了参与免疫反应（白细胞介素（IL）1B）、内源性大麻素信号传导（CNR1）、酸碱平衡（SLC4A3、SLC9A1、SLC9A3）、缝隙连接通道（CX43）和GABA（A）受体转运（PRIP1）的基因的单核苷酸多态性（SNP）。
对照与所有FS患者、单纯性FS患者和复杂性FS患者之间SNP的等位基因频率无显著差异。当将单纯性FS患者根据近亲中有无FS家族史（散发性）分为两组时，IL1B -511 SNP与散发性单纯性FS之间存在显著关联（p=0.003）。
这些数据表明细胞因子基因可能作为FS易感性的增强剂或减弱剂。基因关联研究可能是了解FS分子基础的有效方法，至少在一部分患者亚组中是如此。
