Li Xue, Song Peige, Timofeeva Maria, Meng Xiangrui, Rudan Igor, Little Julian, Satsangi Jack, Campbell Harry, Theodoratou Evropi
Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Colon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit Western General Hospital Edinburgh, Edinburgh, United Kingdom.
Sci Rep. 2016 Sep 27;6:34076. doi: 10.1038/srep34076.
We provide a comprehensive field synopsis of genetic and epigenetic associations for paediatric Inflammatory Bowel Disease (IBD). A systematic review was performed and included 84 genetic association studies reporting data for 183 polymorphisms in 71 genes. Meta-analyses were conducted for 20 SNPs in 10 genes of paediatric Crohn's disease (CD) and for 8 SNPs in 5 genes of paediatric ulcerative colitis (UC). Five epigenetic studies were also included, but formal meta-analysis was not possible. Venice criteria and Bayesian false discovery probability test were applied to assess the credibility of associations. Nine SNPs in 4 genes were considered to have highly credible associations with paediatric CD, of which four variants (rs2066847, rs12521868, rs26313667, rs1800629) were not previously identified in paediatric GWAS. Differential DNA methylation in NOD2 and TNF-α, dysregulated expression in let-7 and miR-124 were associated with paediatric IBD, but not as yet replicated. Highly credible SNPs associated with paediatric IBD have also been implicated in adult IBD, with similar magnitudes of associations. Early onset and distinct phenotypic features of paediatric IBD might be due to distinct epigenetic changes, but these findings need to be replicated. Further progress identifying genetic and epigenetic susceptibility of paediatric IBD will require international collaboration, population diversity and harmonization of protocols.
我们提供了一份关于儿童炎症性肠病（IBD）的遗传和表观遗传关联的全面综述。我们进行了一项系统综述，纳入了84项遗传关联研究，报告了71个基因中183个多态性的数据。对儿童克罗恩病（CD）10个基因中的20个单核苷酸多态性（SNP）以及儿童溃疡性结肠炎（UC）5个基因中的8个SNP进行了荟萃分析。还纳入了5项表观遗传学研究，但无法进行正式的荟萃分析。应用威尼斯标准和贝叶斯错误发现概率检验来评估关联的可信度。4个基因中的9个SNP被认为与儿童CD有高度可信的关联，其中4个变异（rs2066847、rs12521868、rs26313667、rs1800629）此前未在儿童全基因组关联研究（GWAS）中被鉴定出来。NOD2和TNF-α中的DNA甲基化差异、let-7和miR-124的表达失调与儿童IBD相关，但尚未得到重复验证。与儿童IBD相关的高度可信的SNP也与成人IBD有关，且关联程度相似。儿童IBD的早发和独特表型特征可能归因于独特的表观遗传变化，但这些发现需要重复验证。要在确定儿童IBD的遗传和表观遗传易感性方面取得进一步进展，需要国际合作、人群多样性和方案的统一。
