Macrophage migration inhibitory factor and autism spectrum disorders.
Macrophage migration inhibitory factor and autism spectrum disorders.
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DOI：
10.1542/peds.2007-3604
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发表时间：
2008-08
期刊：
影响因子：
8
通讯作者：
Bucala R
中科院分区：
文献类型：
--
作者：
Grigorenko EL;Han SS;Yrigollen CM;Leng L;Mizue Y;Anderson GM;Mulder EJ;de Bildt A;Minderaa RB;Volkmar FR;Chang JT;Bucala R
自闭症谱系障碍 (ASD) 是一种儿童神经发育障碍，其特征是社交和沟通障碍以及重复和刻板行为。巨噬细胞迁移抑制因子 (MIF) 是先天免疫的上游调节因子，通过增加 Toll 样受体的表达并抑制激活诱导的细胞凋亡来促进单核细胞/巨噬细胞激活反应。根据先前的遗传连锁研究结果和报告的 ASD 先天免疫反应改变，我们假设 MIF 可能代表 ASD 或其诊断成分的候选基因。 ASD 和 MIF 之间的遗传关联在来自美国（152 个家庭的 527 名参与者）和荷兰（183 个家庭的 532 名参与者）的两组独立的 ASD 先证者家庭中进行了调查。先证者及其兄弟姐妹（如果有）使用用于 ASD 诊断的临床仪器进行评估。对两个样本中MIF基因启动子区的两个多态性依次进行基因分型。此外，对可获得血浆的荷兰患者子集进行了 MIF 血浆分析。 MIF 启动子的已知功能多态性和 ASD 相关行为之间存在遗传关联。此外，患有 ASD 的先证者表现出比未受影响的兄弟姐妹更高的循环 MIF 水平。血浆中 MIF 的含量与多种 ASD 症状的严重程度相关。这些结果确定 MIF 是 ASD 的易感基因。需要进一步研究 MIF 与 ASD 行为组成部分之间的精确关系、MIF 促进 ASD 发病机制以及 MIF 基因分型的临床应用。
Autism-spectrum disorders (ASD) are childhood neurodevelopmental disorders characterized by social and communicative impairment and repetitive and stereotypical behavior. Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity that promotes monocyte/macrophage activation responses by increasing the expression of Toll-like receptors and inhibiting activation-induced apoptosis. Based on results of prior genetic linkage studies and reported altered innate immune response in ASD, we hypothesized that MIF could represent a candidate gene for ASD or its diagnostic components. Genetic association between ASD and MIF was investigated in two independent sets of families of probands with ASD, from USA (527 participants from 152 families) and Holland (532 participants from 183 families). Probands and their siblings, when available, were evaluated with clinical instruments used for ASD diagnoses. Genotyping was performed for two polymorphisms in the promoter region of the MIF gene in both samples sequentially. In addition, MIF plasma analyses were carried out in a subset of Dutch patients from whom plasma was available. There were genetic associations between known functional polymorphisms in the promoter for MIF and ASD-related behaviors. Also, probands with ASD exhibited higher circulating MIF levels than did their unaffected siblings; the amount of MIF in the plasma correlated with the severity of multiple ASD symptoms. These results identify MIF as a susceptibility gene for ASD. Further research is warranted on the precise relationship between MIF and the behavioral components of ASD, the mechanism by which MIF contributes to ASD pathogenesis, and the clinical utility of MIF genotyping.
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影响因子：
5.2
作者：
Horvath, S;Xu, X;Laird, NM
通讯作者：
Laird, NM
影响因子：
5
作者：
Baugh, JA;Chitnis, S;Bucala, R
通讯作者：
Bucala, R
影响因子：
5.1
作者：
Connolly, AM;Chez, MG;Deuel, RK
通讯作者：
Deuel, RK
DOI：
10.1007/bf01537954
发表时间：
1971-01-01
期刊：
JOURNAL OF AUTISM AND CHILDHOOD SCHIZOPHRENIA
影响因子：
--
作者：
MONEY, J;BOBROW, NA;CLARKE, FC
通讯作者：
CLARKE, FC
影响因子：
64.8
作者：
Chanock, Stephen J.;Manolio, Teri;Collins, Francis S.
通讯作者：
Collins, Francis S.