Hypomorphic MGAT5 polymorphisms promote multiple sclerosis cooperatively with MGAT1 and interleukin-2 and 7 receptor variants
Hypomorphic MGAT5 polymorphisms promote multiple sclerosis cooperatively with MGAT1 and interleukin-2 and 7 receptor variants
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DOI：
10.1016/j.jneuroim.2012.12.008
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发表时间：
2013-03-15
影响因子：
3.3
通讯作者：
Demetriou, Michael
中科院分区：
文献类型：
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作者：
Li, Carey F.;Zhou, Raymond W.;Demetriou, Michael
小鼠中高尔基体N-聚糖分支酶Mgat 5的缺乏促进T细胞过度活跃、CTLA-4的内吞作用和自身免疫，包括自发性多发性硬化（MS）样疾病。多种遗传和环境MS风险因素降低T细胞中的N-聚糖分支。这些包括白细胞介素-2受体-α（IL 2 RA）、白细胞介素-7受体-α（IL 7 RA）和MGAT 1（MGAT 5上游的高尔基体分支酶）的变体，以及维生素D3缺乏和高尔基体底物代谢。在这里，我们描述了与减少的N-聚糖分支、CTLA-4表面表达和MS相关的MGAT 5的连接内含子变体（p = 5.79 x 10（-9），n = 7，741），后者与MGATI、IL 2 RA和IL 7 RA MS风险变体相加（p = 1.76 x 10-9，OR = 0.67 1.83，n = 3，518）。(C)2013爱思唯尔有限公司版权所有。
Deficiency of the Golgi N-glycan branching enzyme Mgat5 in mice promotes T cell hyperactivity, endocytosis of CTLA-4 and autoimmunity, including a spontaneous multiple sclerosis (MS)-like disease. Multiple genetic and environmental MS risk factors lower N-glycan branching in T cells. These include variants in interleukin-2 receptor-alpha (IL2RA), interteukin-7 receptor-alpha (IL7RA), and MGAT1, a Golgi branching enzyme upstream of MGAT5, as well as vitamin D3 deficiency and Golgi substrate metabolism. Here we describe linked intronic variants of MGAT5 that are associated with reduced N-glycan branching, CTLA-4 surface expression and MS (p = 5.79 x 10(-9), n = 7,741), the latter additive with the MGATI, IL2RA and IL7RA MS risk variants (p = 1.76 x 10-9, OR = 0.67 1.83, n = 3,518). (C) 2013 Elsevier B.V. All rights reserved.