Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Department of Urology, University of California, San Francisco, CA, USA.
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Eur Urol Focus. 2017 Feb;3(1):72-81. doi: 10.1016/j.euf.2017.04.010. Epub 2017 May 19.
Urolithiasis has a high prevalence and recurrence rate. Prevention is key to patient management, but risk stratification is challenging. In particular, genetic predisposition for urinary stones is not fully understood.
To review current evidence of potential causative genes for idiopathic urolithiasis and map their relationships to one another. This evidence is essential for future establishment of molecular targeted therapy.
A systematic literature review from 2007 to 2017 was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. The search was restricted to human studies conducted as either case-control or genome-wide association studies, and published in English. We also performed a causal network analysis of candidate genes gained from the systematic review using Ingenuity Pathway Analysis (IPA).
During the systematic screening of literature, 30 papers were selected for the review. A total of 20 genes with 42 polymorphisms/variants were found to be associated with urolithiasis risk. Their functional roles were mainly categorized as stone matrix, calcium and phosphate regulation, urinary concentration and constitution, and inflammation/oxidative stress. IPA network analysis revealed that these genes connected via signaling pathways and a proinflammatory/oxidative environment.
This systematic review provides an updated gene list and novel causal networks for idiopathic urolithiasis risk. Although some genes such as SPP1, CASR, VDR, CLDN14, and SLC34A1 were identified by several studies and recognized by prior reviews, further investigation elucidating their roles in stone formation will be essential for future studies.
In this review, we summarized recent literature regarding genes responsible for kidney stone risk. Based on a detailed review of 30 articles and computational network analysis, we concluded that disorder of mineral regulation with local inflammation in the kidney may cause kidney stone disease.
尿石症的发病率和复发率都很高。预防是患者管理的关键，但风险分层具有挑战性。特别是，遗传易感性对尿石症的影响尚未完全了解。
综述目前关于特发性尿石症潜在致病基因的证据，并对其相互关系进行梳理。这一证据对于未来建立分子靶向治疗至关重要。
按照系统评价和荟萃分析的首选报告项目指南进行了 2007 年至 2017 年的系统文献回顾。检索仅限于以病例对照或全基因组关联研究为基础、用英文发表的人类研究。我们还使用 IPA（Ingenuity Pathway Analysis）对从系统综述中获得的候选基因进行因果网络分析。
在系统筛选文献的过程中，选择了 30 篇论文进行综述。共发现 20 个基因的 42 个多态性/变体与尿石症风险相关。其功能作用主要分为结石基质、钙磷调节、尿液浓缩和组成、炎症/氧化应激。IPA 网络分析显示，这些基因通过信号通路和促炎/氧化环境相互连接。
本系统综述提供了特发性尿石症风险的更新基因列表和新的因果网络。虽然一些基因，如 SPP1、CASR、VDR、CLDN14 和 SLC34A1，已被多项研究确定并为之前的综述所认可，但进一步研究阐明它们在结石形成中的作用对于未来的研究至关重要。
在这篇综述中，我们总结了最近关于导致肾结石风险的基因的文献。通过对 30 篇文章的详细回顾和计算网络分析，我们得出结论，肾脏局部炎症时矿物质调节紊乱可能导致肾结石病。
