Rare variants of RNF213 and moyamoya/non-moyamoya intracranial artery stenosis/occlusion disease risk: a meta-analysis and systematic review.
Rare variants of RNF213 and moyamoya/non-moyamoya intracranial artery stenosis/occlusion disease risk: a meta-analysis and systematic review.
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RNF213 的罕见变异和烟雾病/非烟雾病颅内动脉狭窄/闭塞疾病风险：荟萃分析和系统评价
DOI：
10.1186/s12199-017-0680-1
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发表时间：
2017-11-02
影响因子：
4.7
通讯作者：
Yan J
中科院分区：
文献类型：
--
作者：
Liao X;Deng J;Dai W;Zhang T;Yan J
最近，p.R4810K 和环指蛋白 213 基因 (RNF213) 的其他罕见变异被证明是烟雾病 (MMD) 和非烟雾病颅内动脉狭窄/闭塞病 (ICASO) 的易感性变异。然而，即使在同一种族人群的研究中，p.R4810K 的效应大小也存在很大差异，并且由于样本量小且缺乏重复性，其他罕见变异的确切结论难以捉摸。因此，我们进行这项研究是为了定量评估 RNF213 的罕见变异是否或在多大程度上对不同人群中的 MMD 和 ICASO 有所贡献。截至 2017 年 9 月 5 日，对 PubMed、EMBASE、ISI web of science、CNKI 和万方数据进行了系统检索。使用基于研究间异质性的随机或固定效应模型计算了具有 95% 置信区间 (CI) 的合并比值比 (OR)。按种族和家族史进行亚组分析。进行敏感性和发表偏倚分析以测试关联的稳健性。所有统计分析均使用STATA 12.0进行。本研究纳入 20 项研究，包括 2353 例 MMD 病例和 5488 例对照，以及 11 项研究，包括 1778 例 ICASO 病例和 3140 例对照。汇总 OR 表明，RNF213 p.R4810K 显着增加东亚人的 MMD 和 ICASO 风险，且效应大小差异很大（主导模型：在日本、韩国和中国，MMD 和 ICASO 的比值比分别为 184.04、109.77 和 31.53 以及 10.07、28.52 和 5.59）。它显着增加了日本、韩国和中国的家族性 MMD 风险，其效应大小比每个国家的散发病例大 5 ~ 36 倍（对于家族性病例和散发病例，显性模型 OR 分别为 1802.44、512.42、1109.02 和 134.35、99.82 和 30.52）。 RNF213 p.R4810K对散发性MMD的作用大小在日本和韩国是中国的3~4倍。 RNF213 p.R4810K 还增加了日本和韩国的 ICASO 风险，其效应大小是中国的 2 ~ 4 倍（主导模型 OR 分别为 10.71、28.52 和 5.59）。另外两种罕见变异——p.E4950D 和 p.A5021V 显着增加了中国人群的 MMD 风险（主要模型 OR 分别为 9.06 和 5.01）。在日本、中国、欧洲和西班牙裔美国人人群中发现了 RNF213 的其他各种罕见变异，但尚未有相关证据。这项荟萃分析显示了 RNF213 p.R4810K 在 MMD（尤其是日本、韩国和中国的家族性 MMD 和 ICASO）中的关键作用。除了RNF213 p.R4810K之外，MMD在中国似乎有更复杂的限定词。存在独特的遗传背景，其他环境或遗传因素也可能导致 MMD。需要重点研究 RNF213 变异在 MMD 和 ICASO 中的种族特异性因素和病理作用。本文的在线版本 (10.1186/s12199-017-0680-1) 包含补充材料，可供授权用户使用。
The p.R4810K and other rare variants of ring finger protein 213 gene (RNF213) were illustrated as susceptibility variants for moyamoya (MMD) and non-moyamoya intracranial artery stenosis/occlusion disease (ICASO) recently. However, the effect sizes of p.R4810K were in great discrepancy even in studies of the same ethnic population and firm conclusions of other rare variants have been elusive given the small sample sizes and lack of replication. Thus, we performed this study to quantitatively evaluate whether or to what extent the rare variants of RNF213 contribute to MMD and ICASO in different populations. A systematic search of PubMed, EMBASE, ISI web of science, CNKI, and WANFANG DATA was conducted up to 5 September 2017. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random- or fixed-effect models based on the between-study heterogeneity. The subgroup analyses were performed by the ethnicity and family history. Sensitivity and publication bias analysis were performed to test the robustness of associations. All the statistical analyses were conduct using STATA 12.0. Twenty studies including 2353 MMD cases and 5488 controls and 11 studies including 1778 ICASO cases and 3140 controls were included in this study. Pooled ORs indicated that RNF213 p.R4810K significantly increased MMD and ICASO risk in East Asians with great effect sizes of discrepancy (dominant model: odds ratios 184.04, 109.77, and 31.53 and 10.07, 28.52, and 5.59 for MMD and ICASO, respectively, in Japan, Korea, and China). It significantly increased familial MMD risk in Japan, Korea, and China with 5 ~ 36 times larger effect sizes than that for sporadic ones in each country (dominant model ORs 1802.44, 512.42, 1109.02 and 134.35, 99.82, and 30.52, respectively, for familial and sporadic cases). The effect sizes of RNF213 p.R4810K to sporadic MMD were 3 ~ 4 times larger in Japan and Korea than those in China. RNF213 p.R4810K also increased the ICASO risk in Japan and Korea with 2 ~ 4 times larger effect sizes than that in China (dominant model ORs 10.71, 28.52, and 5.59, respectively). Another two rare variants- p.E4950D and p.A5021V significantly increased MMD risk in Chinese population (dominant model ORs 9.06 and 5.01, respectively). Various other rare variants in RNF213 were identified in Japanese, Chinese, European, and Hispanic American populations without association evidence available yet. This meta-analysis shows the critical roles of RNF213 p.R4810K in MMD especially familial MMD and ICASO in Japan, Korea, and China. Except for RNF213 p.R4810K, MMD seems to have more complex determiners in China. Distinct genetic background exists and other environmental or genetic factor(s) may contribute to MMD. Studies focused on delineating the ethnicity-specific factors and pathological role of RNF213 variants in MMD and ICASO are needed. The online version of this article (10.1186/s12199-017-0680-1) contains supplementary material, which is available to authorized users.
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影响因子：
8.2
作者：
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通讯作者：
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影响因子：
3.7
作者：
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中国人群非烟雾病颅内动脉狭窄/闭塞症RNF213 p.R4810K变异基因分析
影响因子：
4.7
作者：
Zhang T;Guo C;Liao X;Xia J;Wang X;Deng J;Yan J
通讯作者：
Yan J
影响因子：
3.7
作者：
Bang OY;Ryoo S;Kim SJ;Yoon CH;Cha J;Yeon JY;Kim KH;Kim GM;Chung CS;Lee KH;Shin HJ;Ki CS;Jeon P;Kim JS;Hong SC
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影响因子：
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