Lane Brandon M, Cason Rachel, Esezobor Christopher Imokhuede, Gbadegesin Rasheed A
Division of Nephrology, Departments of Pediatrics, Duke University Medical Center, Durham, NC, United States.
Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, United States.
Front Pediatr. 2019 Jan 29;7:8. doi: 10.3389/fped.2019.00008. eCollection 2019.
Advances in genome science in the last 20 years have led to the discovery of over 50 single gene causes and genetic risk loci for steroid resistant nephrotic syndrome (SRNS). Despite these advances, the genetic architecture of childhood steroid sensitive nephrotic syndrome (SSNS) remains poorly understood due in large part to the varying clinical course of SSNS over time. Recent exome and genome wide association studies from well-defined cohorts of children with SSNS identified variants in multiple MHC class II molecules such as HLA-DQA1 and HLA-DQB1 as risk factors for SSNS, thus stressing the central role of adaptive immunity in the pathogenesis of SSNS. However, evidence suggests that unknown second hit risk loci outside of the MHC locus and environmental factors also make significant contributions to disease. In this review, we examine what is currently known about the genetics of SSNS, the implications of recent findings on our understanding of pathogenesis of SSNS, and how we can utilize these results and findings from future studies to improve the management of children with nephrotic syndrome.
过去20年里，基因组科学的进展已促成了50多种导致类固醇抵抗性肾病综合征（SRNS）的单基因病因及遗传风险位点的发现。尽管有这些进展，但儿童类固醇敏感性肾病综合征（SSNS）的遗传结构仍知之甚少，这在很大程度上归因于SSNS随时间变化的临床病程。近期来自定义明确的SSNS患儿队列的外显子组和全基因组关联研究确定了多个MHC II类分子（如HLA-DQA1和HLA-DQB1）中的变异体是SSNS的风险因素，从而强调了适应性免疫在SSNS发病机制中的核心作用。然而，有证据表明，MHC基因座以外未知的二次打击风险位点以及环境因素也对疾病有重大影响。在本综述中，我们探讨了目前对SSNS遗传学的了解、近期研究结果对我们理解SSNS发病机制的意义，以及我们如何利用这些结果和未来研究的发现来改善肾病综合征患儿的管理。
