Tziastoudi Maria, Stefanidis Ioannis, Zintzaras Elias
Department of Biomathematics, University of Thessaly, School of Medicine, Larissa, Greece.
Department of Nephrology, University of Thessaly, School of Medicine, Larissa, Greece.
Clin Kidney J. 2020 Jul 12;13(5):768-781. doi: 10.1093/ckj/sfaa077. eCollection 2020 Oct.
Despite the extensive efforts of scientists, the genetic background of diabetic nephropathy (DN) has not yet been clarified. To elucidate the genetic variants that predispose to the development of DN, we conducted a systematic review and meta-analysis of all available genetic association studies (GAS) of DN. We searched in the Human Genome Epidemiology Navigator (HuGE Navigator) and PubMed for available GAS of DN. The threshold for meta-analysis was three studies per genetic variant. The association between genotype distribution and DN was examined using the generalized linear odds ratio (OR). For variants with available allele frequencies, the examined model was the allele contrast. The pooled OR was estimated using the DerSimonian and Laird random effects model. The publication bias was assessed with Egger's test. We performed pathway analysis of significant genes with DAVID 6.7. Genetic data of 606 variants located in 228 genes were retrieved from 360 GASs and were synthesized with meta-analytic methods. , (), , , , , , , , , , , , (), , , (), , , , , , , , (, , , , , , (), (), (), , , , , , , , , , , , as well as and three intergenic polymorphisms showed significant association with DN. Pathway analysis revealed the overrepresentation of six signalling pathways. The significant findings provide further evidence for genetic factors implication in DN offering new perspectives in discovery of new therapies.
尽管科学家们付出了巨大努力，但糖尿病肾病（DN）的遗传背景仍未明确。为了阐明易导致DN发生的基因变异，我们对所有可用的DN基因关联研究（GAS）进行了系统评价和荟萃分析。我们在人类基因组流行病学导航器（HuGE Navigator）和PubMed中搜索了可用的DN的GAS。荟萃分析的阈值是每个基因变异三项研究。使用广义线性比值比（OR）检验基因型分布与DN之间的关联。对于有可用等位基因频率的变异，所检验的模型是等位基因对比。使用DerSimonian和Laird随机效应模型估计合并的OR。用Egger检验评估发表偏倚。我们使用DAVID 6.7对显著基因进行通路分析。从360项GAS中检索了位于228个基因中的606个变异的遗传数据，并用荟萃分析方法进行了综合。……以及三个基因间多态性与DN显示出显著关联。通路分析揭示了六个信号通路的过度表达。这些重要发现为DN中遗传因素的作用提供了进一步证据，为发现新疗法提供了新的视角。
