Department of Clinical Neuroscience, Institute of Psychiatry, King's College London, de Crespigny Park, Denmark Hill, London, United Kingdom.
Epilepsia. 2010 Apr;51(4):694-8. doi: 10.1111/j.1528-1167.2009.02473.x. Epub 2009 Dec 22.
We have investigated seven voltage-gated sodium channel genes for association with idiopathic generalized epilepsy (IGE). Probands and control DNA were grouped into pools and used to screen 85 single-nucleotide polymorphisms (SNPs), mostly HapMap SNPs tagging the common variation in these genes. Twelve SNPs exhibiting an allele frequency difference between pools were genotyped individually in our sample of 232 probands, 313 controls, and 95 parent-proband trios. Two SNPs, in SCN1A and SCN8A, were associated by allele and genotype at nominal level of significance, but were not significant after Bonferroni correction. Two SCN2A SNPs (rs3943809 and rs16850331) were associated by case-control with a subgroup with IGE and history of febrile seizures and also by transmission disequilibrium test (TDT) in parent-proband trios. Both SNPs are part of a linkage disequilibrium (LD) cluster of 38 SNPs, but none are obvious functional variants. The association of rs3943809 with the febrile seizure subgroup (p = 0.0004) remains significant after the conservative Bonferroni correction for multiple testing.
我们研究了七个电压门控钠离子通道基因与特发性全面性癫痫（IGE）的关联。先将先证者和对照的 DNA 分成池，然后用其来筛选 85 个单核苷酸多态性（SNP），这些 SNP 主要是用来标记这些基因中的常见变异的 HapMap SNP。在我们的 232 名先证者、313 名对照和 95 个父母-子女三体型样本中，对 12 个在池之间表现出等位基因频率差异的 SNP 进行了单独的基因分型。在名义显著性水平上，SCN1A 和 SCN8A 中的两个 SNP 通过等位基因和基因型相关，但在 Bonferroni 校正后不显著。两个 SCN2A SNPs（rs3943809 和 rs16850331）通过病例对照与 IGE 和热性惊厥史亚组相关，并且通过父母-子女三体型的传递不平衡测试（TDT）也相关。这两个 SNP 均为 38 个连锁不平衡（LD）簇的一部分，但都不是明显的功能变体。rs3943809 与热性惊厥亚组的关联（p = 0.0004）在对多重测试进行保守的 Bonferroni 校正后仍然显著。
