Chou I-Ching, Peng Ching-Tien, Huang Chao-Ching, Tsai Jeffrey J P, Tsai Fuu-Jen, Tsai Chang-Hai
Department of Pediatrics, China Medical College Hospital, Taichung, Taiwan.
Pediatr Res. 2003 Jul;54(1):26-9. doi: 10.1203/01.PDR.0000069696.96041.34. Epub 2003 Apr 2.
An alternation of gamma-aminobutyric acid (GABA)-ergic neurotransmission has been implicated as an etiologic factor in epileptogenesis. Missense mutations in the GABRG2 gene, which encodes the gamma2 subunit of central nervous GABAA receptors, have recently been described in one family with childhood absence epilepsy and febrile seizures (FSs). FSs represent the majority of childhood seizures and have a genetic predisposition. It is not known, however, whether polymorphisms in those genes involved in familial epilepsies also contribute to the pathogenesis of FSs. By performing an association study, we used single-nucleotide polymorphisms to investigate the distribution of genotypes of GABRG2 in patients with FSs. A total of 104 children with FSs and 83 normal control subjects were included in the study. PCR was used to identify the C/T and A/G polymorphisms of the GABRG2 gene on chromosome 5q33. Genotypes and allelic frequencies for the GABRG2 gene polymorphisms in both groups were compared. The GABRG2 (nucleotide position 3145 in intron G-->A) gene in both groups was not significantly different. In contrast, the number of individuals with the GABRG2 (SNP211037)-C/C genotype in patients with FSs was significantly greater compared with that in healthy control subjects (p = 0.017), and the GABRG2 (SNP211037)-C allele frequency in patients with FSs was significantly higher than that in healthy control subjects (p = 0.009). The odds ratio for developing FSs in individuals with the GABRG2 (SNP211037)-C/C genotype was 2.56 compared with individuals with the GABRG2 (SNP211037)-T/T genotype. These data suggest that the GABRG2 gene might be one of the susceptibility factors for FSs.
γ-氨基丁酸（GABA）能神经传递的改变被认为是癫痫发生的一个病因。编码中枢神经系统GABAA受体γ2亚基的GABRG2基因中的错义突变，最近在一个患有儿童失神癫痫和热性惊厥（FSs）的家族中被发现。FSs是儿童癫痫发作的主要类型，具有遗传易感性。然而，尚不清楚那些与家族性癫痫相关的基因中的多态性是否也参与FSs的发病机制。通过进行一项关联研究，我们使用单核苷酸多态性来调查FSs患者中GABRG2基因的基因型分布。该研究共纳入了104例FSs儿童和83名正常对照受试者。采用聚合酶链反应（PCR）来鉴定5号染色体q33上GABRG2基因的C/T和A/G多态性。比较了两组中GABRG2基因多态性的基因型和等位基因频率。两组中GABRG2（内含子G中核苷酸位置3145，G→A）基因无显著差异。相比之下，FSs患者中具有GABRG2（SNP211037）-C/C基因型的个体数量显著多于健康对照受试者（p = 0.017），且FSs患者中GABRG2（SNP211037）-C等位基因频率显著高于健康对照受试者（p = 0.009）。与具有GABRG2（SNP211037）-T/T基因型的个体相比，具有GABRG2（SNP211037）-C/C基因型的个体发生FSs的优势比为2.56。这些数据表明，GABRG2基因可能是FSs的易感因素之一。
