Chioza B, Osei-Lah A, Wilkie H, Nashef L, McCormick D, Asherson P, Makoff A J
Department of Psychological Medicine, Institute of Psychiatry, Denmark Hill, London, UK.
Epilepsy Res. 2002 Dec;52(2):107-16. doi: 10.1016/s0920-1211(02)00195-x.
Several potassium channel genes have been implicated in epilepsy. We have investigated three such genes, KCNJ3, KCNJ6 and KCNQ2, by association studies using a broad sample of idiopathic generalised epilepsy (IGE) unselected by syndrome. One of the two single nucleotide polymorphisms (SNPs) examined in one of the inward rectifying potassium channel genes, KCNJ3, was associated with IGE by genotype (P=0.0097), while its association by allele was of borderline significance (P=0.051). Analysis of the different clinical subgroups within the IGE sample showed more significant association with the presence of absence seizures (P=0.0041) and which is still significant after correction for multiple testing. Neither SNP in the other rectifying potassium channel gene, KCNJ6, was associated with IGE or any subgroup. None of the three SNPs in the voltage-gated potassium channel gene, KCNQ2, was associated with IGE. However, one SNP was associated with epilepsy with generalised tonic clonic seizures only (P=0.016), as was an SNP approximately 56 kb distant in the closely linked nicotinic acetylcholine gene CHRNA4 (P=0.014). These two SNPs were not in linkage disequilibrium with each other, suggesting that if they are not true associations they have independently occurred by chance. Neither association remains significant after correcting for multiple testing.
几个钾通道基因已被证实与癫痫有关。我们通过关联研究调查了三个这样的基因，即KCNJ3、KCNJ6和KCNQ2，研究样本为未经综合征选择的广泛的特发性全身性癫痫（IGE）患者。在内向整流钾通道基因之一KCNJ3中检测的两个单核苷酸多态性（SNP）之一，通过基因型与IGE相关（P = 0.0097），而其等位基因关联具有临界显著性（P = 0.051）。对IGE样本中不同临床亚组的分析显示，与失神发作的存在有更显著的关联（P = 0.0041），在多重检验校正后仍然显著。另一个整流钾通道基因KCNJ6中的两个SNP均与IGE或任何亚组无关。电压门控钾通道基因KCNQ2中的三个SNP均与IGE无关。然而，一个SNP仅与伴有全身强直阵挛发作的癫痫相关（P = 0.016），在紧密连锁的烟碱型乙酰胆碱基因CHRNA4中距离约56 kb处的一个SNP也是如此（P = 0.014）。这两个SNP彼此不存在连锁不平衡，表明如果它们不是真正的关联，那么它们是偶然独立出现的。在多重检验校正后，这两种关联均不再显著。
