Common variants associated with general and MMR vaccine-related febrile seizures.
Common variants associated with general and MMR vaccine-related febrile seizures.
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DOI：
10.1038/ng.3129
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发表时间：
2014-12
期刊：
影响因子：
30.8
通讯作者：
Hviid, Anders
中科院分区：
文献类型：
--
作者：
Feenstra, Bjarke;Pasternak, Bjorn;Geller, Frank;Carstensen, Lisbeth;Wang, Tongfei;Huang, Fen;Eitson, Jennifer L.;Hollegaard, Mads V.;Svanstrom, Henrik;Vestergaard, Mogens;Hougaard, David M.;Schoggins, John W.;Jan, Lily Yeh;Melbye, Mads;Hviid, Anders
热性惊厥是麻疹、腮腺炎和风疹（MMR）疫苗接种后公认的严重不良事件。我们进行了一系列全基因组关联扫描，比较与mmr相关的热性惊厥儿童、与疫苗接种无关的热性惊厥儿童和无热性惊厥史的对照组。两个基因座与mmr相关的热性惊厥明显相关，包含干扰素刺激基因IFI44L （rs273259；与对照组相比P = 5.9×10−12；与mmr无关的热性惊厥相比P =1.2×10−9）和麻疹病毒受体CD46 （rs1318653；与对照组相比P = 9.6×10−11；与mmr无关的热性惊厥相比P = 1.6×10−9）。此外，四个位点与热性惊厥相关，涉及钠通道基因SCN1A （rs6432860, P = 2.2×10−16）和SCN2A (rs3769955, P = 3.1×10−10)，TMEM16家族基因（TMEM16C, rs114444506, P = 3.7×10−20），以及与镁水平相关的区域（12q21.33, rs11105468, P = 3.4×10−11）。最后，通过电生理实验在野生型和敲除型大鼠中证明了TMEM16C的功能相关性。
Febrile seizures represent a recognized serious adverse event following measles, mumps, and rubella (MMR) vaccination. We conducted a series of genome-wide association scans comparing children with MMR-related febrile seizures, children with febrile seizures unrelated to vaccination, and controls with no history of febrile seizures. Two loci were distinctly associated with MMR-related febrile seizures, harboring the interferon-stimulated gene IFI44L (rs273259; P = 5.9×10−12 vs. controls; P =1.2×10−9 vs. MMR-unrelated febrile seizures) and the measles virus receptor CD46 (rs1318653; P = 9.6×10−11 vs. controls; P = 1.6×10−9 vs. MMR-unrelated febrile seizures). Furthermore, four loci were associated with febrile seizures in general implicating the sodium channel genes SCN1A (rs6432860; P = 2.2×10−16) and SCN2A (rs3769955; P = 3.1×10−10), a TMEM16 family gene (TMEM16C; rs114444506; P = 3.7×10−20), and a region associated with magnesium levels (12q21.33; rs11105468; P = 3.4×10−11). Finally, functional relevance of TMEM16C was demonstrated with electrophysiological experiments in wild-type and knockout rats.
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