A Rare Variant (rs933717) at FBXO31-MAP1LC3B in Chinese Is Associated With Systemic Lupus Erythematosus.
A Rare Variant (rs933717) at FBXO31-MAP1LC3B in Chinese Is Associated With Systemic Lupus Erythematosus.
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中文 FBXO31-MAP1LC3B 的罕见变异 (rs933717) 与系统性红斑狼疮相关。
DOI：
10.1002/art.40353
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Qi YY;Zhou XJ;Nath SK;Sun C;Wang YN;Hou P;Mu R;Li C;Guo JP;Li ZG;Wang G;Xu HJ;Hao YJ;Zhang ZL;Yue WH;Zhang H;Zhao MH;Zhang H
最近来自遗传学、细胞生物学和模式动物研究的证据表明，自噬在介导系统性红斑狼疮(SLE)中起着关键作用。然而，遗传基础还没有得到彻底的研究。因此，本研究的目的是确定自噬相关基因中的其他易感变异及其功能意义。首先，我们使用免疫芯片对SLE患者进行了基于基因家族的遗传关联分析，并选择了最相关的多态在其他队列中进行复制。为了确定调控线索，我们分析了公开可用的血液表达数量性状基因座数据和DNA元素百科全书数据中转录因子结合位点和细胞类型特异性差异表达的数据。通过荧光素酶报告实验、凝胶迁移率改变分析(EMSA)和差异基因表达分析检测其功能效应。在14,474例样本中，我们观察到罕见的中国突变rs933717T与系统性红斑狼疮的易感性相关(病例0.11%，对照0.87%，p=2.36×10−10，OR=0.13)。Rs933717风险等位基因C与MAP1LC3B表达增加相关：在SLE患者和狼疮易感小鼠中观察到MAP1LC3B基因表达增加。在报告基因结构中，在HEK 293T和Jurkat细胞系中，危险等位基因使荧光素酶活性增加了2.7~3.8倍，HEK293T和Jurkat核提取液与危险等位基因的结合也增加。我们观察到广泛使用的自噬标记LC3B与SLE易感性之间可能存在遗传关联。
Recent evidence from genetic, cell biology and model animal studies have suggested a pivotal role of autophagy in mediating systemic lupus erythematosus (SLE). However, the genetic basis has not yet been thoroughly examined. The aim of the present study was therefore to identify additional susceptibility variants in autophagy-related genes, and their functional significance. First, we performed a gene family-based genetic association analysis in patients with SLE using ImmunoChip, and selected the top-associated polymorphisms for replication in additional cohorts. To identify regulatory clues, we analyzed publicly available blood expression quantitative trait locus data and Encyclopedia of DNA Elements data on transcription factor binding sites and cell type-specific differential expression. The functional effects were tested by luciferase reporter assays, electrophoretic mobility gel shift assays (EMSA) and differential gene expression assays. In 14,474 samples, we observed that the rare Chinese variant rs933717T was associated with susceptibility to SLE (case 0.11% vs. control 0.87%, p = 2.36 × 10−10, OR = 0.13). The rs933717 risk allele C correlated with increased MAP1LC3B expression: increased MAP1LC3B mRNA was observed in patients with SLE and in lupus-prone mice. In reporter gene constructs, the risk allele increased luciferase activity up to 2.7~3.8-fold in both HEK 293T and Jurkat cell lines, and the binding of HEK293T and Jurkat nuclear extracts to the risk allele was also increased. We observed a likely genetic association between LC3B, a widely-used marker for autophagy, and susceptibility to SLE.
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DOI：
10.1084/jem.20061303
发表时间：
2007-01-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Pua HH;Dzhagalov I;Chuck M;Mizushima N;He YW
通讯作者：
He YW
免疫相关位点的高密度基因分型识别出亚洲血统个体中新的 SLE 风险变异
影响因子：
30.8
作者：
Sun C;Molineros JE;Looger LL;Zhou XJ;Kim K;Okada Y;Ma J;Qi YY;Kim-Howard X;Motghare P;Bhattarai K;Adler A;Bang SY;Lee HS;Kim TH;Kang YM;Suh CH;Chung WT;Park YB;Choe JY;Shim SC;Kochi Y;Suzuki A;Kubo M;Sumida T;Yamamoto K;Lee SS;Kim YJ;Han BG;Dozmorov M;Kaufman KM;Wren JD;Harley JB;Shen N;Chua KH;Zhang H;Bae SC;Nath SK
通讯作者：
Nath SK
非规范自噬抑制自身炎症，类似狼疮的对垂死细胞的反应。
影响因子：
64.8
作者：
Martinez J;Cunha LD;Park S;Yang M;Lu Q;Orchard R;Li QZ;Yan M;Janke L;Guy C;Linkermann A;Virgin HW;Green DR
通讯作者：
Green DR
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
32.4
作者：
Henault J;Martinez J;Riggs JM;Tian J;Mehta P;Clarke L;Sasai M;Latz E;Brinkmann MM;Iwasaki A;Coyle AJ;Kolbeck R;Green DR;Sanjuan MA
通讯作者：
Sanjuan MA