Schlachter K, Gruber-Sedlmayr U, Stogmann E, Lausecker M, Hotzy C, Balzar J, Schuh E, Baumgartner C, Mueller J C, Illig T, Wichmann H E, Lichtner P, Meitinger T, Strom T M, Zimprich A, Zimprich F
Department of Pediatrics, LKH Bregenz, Austria.
Neurology. 2009 Mar 17;72(11):974-8. doi: 10.1212/01.wnl.0000344401.02915.00.
Our aim was to investigate whether the risk of febrile seizures is influenced by a common functional polymorphism in the sodium channel gene SCN1A. This single nucleotide polymorphism (IVS5N+5 G>A, rs3812718) was shown to modify the proportion of two alternative transcripts of the channel.
We performed an exploratory case-control association analysis in 90 adult epilepsy patients with childhood febrile seizures vs 486 epilepsy patients without a history of febrile seizures and also vs 701 population controls. In the replication step, we investigated children with febrile seizures without concomitant epilepsy at the time of their inclusion. We compared the genotypes of 55 of those children against population controls and performed a within-family association analysis in an additional 88 child-parent trios with febrile seizures.
We observed a significant association of the splice-site interrupting A-allele with febrile seizures (p value in the exploratory step: 0.000017; joint p value of the replication: 0.00069). Our data suggest that the A-allele of this variant confers a threefold genotype relative risk in homozygotes and accounts for a population attributable fraction of up to 50% for the etiology of febrile seizures.
The A-allele of the SCN1A single nucleotide polymorphism IVS5N+5 G>A (rs3812718) represents a common and relevant risk factor for febrile seizures. A limitation of the present study is that patients of the exploratory and replication steps differed in aspects of their phenotype (febrile seizures with and without additional epilepsy).
我们的目的是研究钠通道基因SCN1A中一种常见的功能多态性是否会影响热性惊厥的风险。这种单核苷酸多态性（IVS5N+5 G>A，rs3812718）已被证明可改变该通道两种可变转录本的比例。
我们对90例有儿童期热性惊厥的成年癫痫患者与486例无热性惊厥病史的癫痫患者以及701名人群对照进行了探索性病例对照关联分析。在重复验证阶段，我们纳入了热性惊厥但无癫痫的儿童进行研究。我们将其中55名儿童的基因型与人群对照进行比较，并在另外88个有热性惊厥的儿童-父母三联体中进行家系内关联分析。
我们观察到剪接位点中断A等位基因与热性惊厥之间存在显著关联（探索性阶段p值：0.000017；重复验证阶段联合p值：0.00069）。我们的数据表明，该变体的A等位基因在纯合子中赋予三倍的基因型相对风险，并且在热性惊厥病因中占高达50%的人群归因分数。
SCN1A单核苷酸多态性IVS5N+5 G>A（rs3812718）的A等位基因是热性惊厥的一个常见且相关的风险因素。本研究的一个局限性是探索性和重复验证阶段的患者在表型方面存在差异（有无额外癫痫的热性惊厥）。
