Shibata Akiko, Kasai Mariko, Hoshino Ai, Mizuguchi Masashi
Department of Developmental Medical Sciences, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Front Neurol. 2022 May 30;13:891721. doi: 10.3389/fneur.2022.891721. eCollection 2022.
Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a severe neurologic complication of febrile infectious diseases in children. At the onset, AESD is clinically manifested as febrile status epilepticus. Subsequent damage to the cerebral cortex is ascribed to neurotoxicity. The incidence of AESD is remarkably high in Japan, suggesting the involvement of genetic factors. The expression of interleukin 1 beta (IL-1β), a member of the cytokine family involved in the inflammatory response, is reportedly associated with rs16944, a polymorphism in the upstream region of the gene, being higher in TT genotype. Previous association studies of rs16944 with febrile seizures (FS) have demonstrated a significant excess in the TT vs. CC + CT genotype in the Asian population. Here, we conducted a case-control association study of rs16944 in AESD.
We genotyped rs16944 by Sanger sequencing on 283 patients with AESD. As controls, we used genotyping data of 104 Japanese individuals obtained from the 1,000 Genomes Project. Then, we performed a case-control association study using the chi-square test.
The ratio of individuals with TT vs. those with CC+CT genotype was significantly lower in AESD than in the controls [-value 0.021, Odds Ratio (OR) 0.52]. This finding was opposite to that of a previously reported FS.
The AESD has a genetic background distinct from FS and is not a severe type of FS.
伴有双相性癫痫发作和晚期弥散降低的急性脑病（AESD）是儿童发热性传染病的一种严重神经并发症。在发病初期，AESD临床表现为热性惊厥持续状态。随后的大脑皮质损伤归因于神经毒性。AESD在日本的发病率显著较高，提示存在遗传因素。据报道，参与炎症反应的细胞因子家族成员白细胞介素1β（IL-1β）的表达与该基因上游区域的一个多态性rs16944相关，TT基因型中的表达更高。先前关于rs16944与热性惊厥（FS）的关联研究表明，在亚洲人群中，TT基因型与CC + CT基因型相比有显著过量。在此，我们进行了一项关于rs16944与AESD的病例对照关联研究。
我们通过桑格测序对283例AESD患者的rs16944进行基因分型。作为对照，我们使用了从千人基因组计划获得的104名日本个体的基因分型数据。然后，我们使用卡方检验进行病例对照关联研究。
AESD中TT基因型个体与CC + CT基因型个体的比例显著低于对照组[P值0.021，优势比（OR）0.52]。这一发现与先前报道的FS相反。
AESD具有与FS不同的遗传背景，并非FS的严重类型。
