(一)中文摘要 研究背景與目的: 熱性痙攣是常見的兒科疾病，發生率約為 2-5%。熱性痙攣的 起因很複雜，包含了先天基因及後天環境因素，事實上, 熱性痙攣的致病機轉 至今仍不明。最近的研究中,在家族遺傳性癲癎的基因變異已有重大突破。包括 神經性菸鹼乙膽素接受器,γ-胺基丁酸接受器,電壓差閘門鈉離子通道, 與電壓 差閘門鉀離子通道等的基因變異, 均已發現可引發不同型態的家族遺傳性癲 癎。根據我們實驗室過去的研究基礎,我們利用單核酸多形性(single nucleotide polymorphisms; SNPs)為工具,以 SNP 為標記尋找熱性痙攣與家族 遺傳性癲癎相關聯基因是否有共同之基因變異。 實驗方法: 以中國醫藥大學附設醫院小兒神經科,就診的熱性痙攣的臺灣病童 為實驗對象。病童的診斷條件符合 1989 年國際抗癲癎聯盟之診斷條件。對照組 收集亦在同家醫院,同為臺灣人種族,家族不相關聯,且無癲癎或熱性痙攣之家 族史者。總數為 104 名病童與 83 比名對照組。多形性基因包括γ-胺基丁酸接 受器,電壓差閘門鈉離子通道,電壓差閘門鉀離子通道與神經性菸鹼乙膽素接受器 等.以 polymerase chain reaction 的方式分析。兩組的基因型分布與對偶質的 頻率相比。
結果:我們發現 ion channel receptor 基因中的神經性菸鹼乙膽素接受器與 γ-胺基丁酸接受器在實驗組與對照組的差異達到統計上的意義(P<0.05)。而電壓 差閘門鈉離子通道與電壓差閘門鉀離子通道, 在實驗組與對照組的差異並無統 計上的意義 結論: 神經性菸鹼乙膽素接受器與 γ-胺基丁酸接受器與熱性痙攣有相關聯。這 不僅可以提供吾人對熱性痙攣成因的認識，更可提供將來對其他痙攣疾病新的 治療與預防方向。 關鍵詞：熱性痙攣、單核酸多形性、神經性菸鹼乙膽素接受器、γ-胺基丁酸 接受器、ion channel
(二)英文摘要
Objective: Febrile convulsions (FCs), the most common form of childhood seizures,
occurs in 2~5% of children. The FCs is a complex disease, but the etiology is
unknown. A genetic predisposition plays a major role in the etiology of the FCs.
Three types of familial epilepsies have been linked to mutations in human genes
encoding subunits of the neuronal nicotinic acetylcholine receptor (α4, CHRNA4, and
β2, CHRNB2, subunits), the voltage-gated potassium (KCNQ2, KCNQ3), the
γ–aminobutyric acid receptor genes (GABRG2) and the voltage-gated sodium
(SCN1A, SCN1B) channels. The familial epilepsy and FCs may share a common
etiology. Base on our previous experience, the SNP marker provides a new way for
the identification of complex gene-associated diseases such as FCs.
Methods: A total of 104 patients with FCs and 83 normal control subjects were
included. Cases were matched with controls according to age, sex, ethnicity and
geographic location of origin. Diagnosis of FCs followed the criteria established in
the 1989 International Classification of Epileptic Syndromes. The ion channel
receptor genes, includingγ–aminobutyric acid receptor genes (GABRG2),
voltage-gated sodium channel subunit genes (SCN1B, SCN1A), voltage-gated
potassium channel genes (KCNQ2 and KCNQ3), and neuronal nicotinic acetylcholine
receptor (nAChR) genes (CHRNA4 and CHRNB2) were identified by polymerase
Results: There was no significant difference in the distribution of genotypes and
allelic frequencies between both groups for SCN1B, SCN1A, KCNQ2, KCNQ3 and
CHRNB2 genes. However, there were significant different in the distribution of
genotypes and allelic frequencies between both groups for CHRNA4 and GABRG2.
Conclusions: These data suggest that the SCN1B, SCN1A, KCNQ2, KCNQ3 and
CHRNB2 genes might not be one of the susceptibility factors for FCs. In contrast,
this results suggest that the CHRNA4 gene, the GABRG2 gene, or a closely linked
gene might be one of the susceptibility factors for FCs. It is possible considered that
the CHRNA4 gene and the GABRG2 gene polymorphisms are useful markers for
prediction of the susceptibility of FCs of children.
Key words: febrile convulsions, SNP, γ–aminobutyric acid receptor gene, neuronal
nicotinic acetylcholine receptor gene, ion channel.
