Cytokine-related and sodium channel polymorphism as candidate predisposing factors for childhood encephalopathy FIRES/AERRPS
Cytokine-related and sodium channel polymorphism as candidate predisposing factors for childhood encephalopathy FIRES/AERRPS
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DOI：
10.1016/j.jns.2016.07.040
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发表时间：
2016-09-15
影响因子：
4.4
通讯作者：
Mizuguchi, M.
中科院分区：
文献类型：
--
作者：
Saitoh, M.;Kobayashi, K.;Mizuguchi, M.
发热性感染相关癫痫综合征（FIRES），或急性脑炎伴难治性反复部分性癫痫发作（AERRPS），是一种以发热介导的癫痫发作为首发症状的癫痫性脑病。病因尚不清楚。为了阐明FIRES/AERRPS（以下简称FIRES）的遗传背景，我们招募了19名日本患者，对IL 1B、IL 6、IL 10、TNFA、IL 1 RN、SCN 1A和SCN 2A基因多态性进行了基因分型，并比较了患者和对照组之间的频率。对于IL 1 RN，患者中可变数目串联重复（VNTR）等位基因RN 2的频率显著高于对照组（p = 0.0067），IL 1 RN 5'上游rs 4251981处的A等位基因具有临界显著性（p = 0.015）。含有RN 2的单倍型与FIRES风险增加相关（OR 3.88，95%CI 1.40-10.8，p = 0.0057）。对于SCN 1A，没有多态性显示出显著的关联，而错义突变R1575 C在两名患者中被发现。对于SCN 2A，rs 1864885处G等位基因的次要等位基因频率在患者中较高，具有临界显著性（p = 0.011）。我们证明了包含RN 2的IL 1 RN单倍型与FIRES的关联，并显示了在日本患者中IL 1 RN rs 4251981 G > A和SCN 2A rs 1864885 A > G的可能关联。这些初步研究结果表明，多种遗传因素参与了FIRES，这需要通过未来在更多FIRES病例中的研究来证实。(C)2016爱思唯尔B. V.保留所有权利。
Febrile infection-related epilepsy syndrome (FIRES), or acute encephalitis with refractory, repetitive partial seizures (AERRPS), is an epileptic encephalopathy beginning with fever-mediated seizures. The etiology remains unclear. To elucidate the genetic background of FIRES/AERRPS (hereafter FIRES), we recruited 19 Japanese patients, genotyped polymorphisms of the IL1B, IL6, IL10, TNFA, IL1RN, SCN1A and SCN2A genes, and compared their frequency between the patients and controls. For IL1RN, the frequency of a variable number of tandem repeat (VNTR) allele, RN2, was significantly higher in the patients than in controls (p = 0.0067), and A allele at rs4251981 in 5' upstream of IL1RN with borderline significance (p = 0.015). Haplotype containing RN2 was associated with an increased risk of FIRES (OR 3.88, 95%CI 1.40-10.8, p = 0.0057). For SCN1A, no polymorphisms showed a significant association, whereas a missense mutation, R1575C, was found in two patients. For SCN2A, the minor allele frequency of G allele at rs1864885 was higher in patients with borderline significance (p = 0.011).We demonstrated the association of IL1RN haplotype containing RN2 with FIRES, and showed a possible association of IL1RN rs4251981 G > A and SCN2A rs1864885 A > G, in Japanese patients. These preliminary findings suggest the involvement of multiple genetic factors in FIRES, which needs to be confirmed by future studies in a larger number of FIRES cases. (C) 2016 Elsevier B.V. All rights reserved.