Genetic associations for keratoconus: a systematic review and meta-analysis.
Genetic associations for keratoconus: a systematic review and meta-analysis.
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DOI：
10.1038/s41598-017-04393-2
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发表时间：
2017-07-04
影响因子：
4.6
通讯作者：
Chen LJ
中科院分区：
文献类型：
--
作者：
Rong SS;Ma STU;Yu XT;Ma L;Chu WK;Chan TCY;Wang YM;Young AL;Pang CP;Jhanji V;Chen LJ
圆锥角膜的遗传关联可能有助于了解疾病的发病机制和发现早期发现疾病的生物标志物。我们进行了一项系统回顾和荟萃分析，总结了所有报道的与该疾病相关的遗传学。我们在MEDLINE、Embase、Web of Science和HuGENET数据库中检索了1950年至2016年6月发表的圆锥角膜遗传学研究。所有多态性的总体优势比和95%置信区间采用随机效应模型进行估计。在检索到的639篇报告中，24篇符合荟萃分析的合格研究标准，涉及28个基因/位点的53个多态性。我们的荟萃分析的结果导致在白人圆锥角膜的6个基因/位点的8个单核苷酸多态性（SNP）的优先顺序。其中5个基因/位点最初是在全基因组关联研究中发现的，包括FOXO 1（rs2721051，P = 5.6 × 10−11），RXRA-COL5A1（rs1536482，P = 2.5 × 10−9），FNDC3B（rs4894535，P = 1.4 × 10−8）、IMMP2L（rs757219，P = 6.1 × 10−7; rs214884，P = 2.3 × 10−5）和BANP-ZNF 469（rs9938149，P = 1.3 × 10−5）。基因COL 4A 4（rs 2229813，P = 1.3 × 10−12; rs 2228557，P = 4.5 × 10−7）在先前的候选基因研究中被确定。我们还在10个基因/位点中发现了具有汇总P值< 0.05的SNP。敏感性分析表明，结果是稳健的。复制研究和了解这些基因在圆锥角膜中的作用是必要的。
Genetic associations for keratoconus could be useful for understanding disease pathogenesis and discovering biomarkers for early detection of the disease. We conducted a systematic review and meta-analysis to summarize all reported genetic associations for the disease. We searched in the MEDLINE, Embase, Web of Science, and HuGENET databases for genetic studies of keratoconus published from 1950 to June 2016. The summary odds ratio and 95% confidence intervals of all polymorphisms were estimated using the random-effect model. Among 639 reports that were retrieved, 24 fulfilled required criteria as eligible studies for meta-analysis, involving a total of 53 polymorphisms in 28 genes/loci. Results of our meta-analysis lead to the prioritization of 8 single-nucleotide polymorphisms (SNPs) in 6 genes/loci for keratoconus in Whites. Of them 5 genes/loci were originally detected in genome-wide association studies, including FOXO1 (rs2721051, P = 5.6 × 10−11), RXRA-COL5A1 (rs1536482, P = 2.5 × 10−9), FNDC3B (rs4894535, P = 1.4 × 10−8), IMMP2L (rs757219, P = 6.1 × 10−7; rs214884, P = 2.3 × 10−5), and BANP-ZNF469 (rs9938149, P = 1.3 × 10−5). The gene COL4A4 (rs2229813, P = 1.3 × 10−12; rs2228557, P = 4.5 × 10−7) was identified in previous candidate gene studies. We also found SNPs in 10 genes/loci that had a summary P value < 0.05. Sensitivity analysis indicated that the results were robust. Replication studies and understanding the roles of these genes in keratoconus are warranted.