与普通及与MMR疫苗相关的热性惊厥相关的常见变异体。
Common variants associated with general and MMR vaccine-related febrile seizures.
作者信息
Feenstra Bjarke, Pasternak Björn, Geller Frank, Carstensen Lisbeth, Wang Tongfei, Huang Fen, Eitson Jennifer L, Hollegaard Mads V, Svanström Henrik, Vestergaard Mogens, Hougaard David M, Schoggins John W, Jan Lily Yeh, Melbye Mads, Hviid Anders
机构信息
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
1] Department of Physiology, University of California, San Francisco, San Francisco, California, USA. [2] Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA. [3] Howard Hughes Medical Institute, San Francisco, California, USA.
出版信息
Nat Genet. 2014 Dec;46(12):1274-82. doi: 10.1038/ng.3129. Epub 2014 Oct 26.
Febrile seizures represent a 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) versus controls, P = 1.2 × 10(-9) versus MMR-unrelated febrile seizures) and the measles virus receptor CD46 (rs1318653: P = 9.6 × 10(-11) versus controls, P = 1.6 × 10(-9) versus 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 (ANO3; rs114444506: P = 3.7 × 10(-20)) and a region associated with magnesium levels (12q21.33; rs11105468: P = 3.4 × 10(-11)). Finally, we show the functional relevance of ANO3 (TMEM16C) with electrophysiological experiments in wild-type and knockout rats.
热性惊厥是麻疹、腮腺炎和风疹（MMR）疫苗接种后的一种严重不良事件。我们进行了一系列全基因组关联扫描，比较了患有MMR相关热性惊厥的儿童、患有与疫苗接种无关的热性惊厥的儿童以及无热性惊厥病史的对照组。有两个基因座与MMR相关热性惊厥显著相关，分别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，有四个基因座总体上与热性惊厥相关，涉及钠通道基因SCN1A（rs6432860：P = 2.2 × 10^(-16)）和SCN2A（rs3769955：P = 3.1 × 10^(-10)）、一个跨膜蛋白16家族基因（ANO3；rs114444506：P = 3.7 × 10^(-20)）以及一个与镁水平相关的区域（12q21.33；rs11105468：P = 3.4 × 10^(-11)）。最后，我们通过在野生型和基因敲除大鼠中进行电生理实验展示了ANO3（跨膜蛋白16C）的功能相关性。
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