Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.; Key Laboratory of Nephrology, National Health Commission (NHC) and Guangdong Province, Guangzhou, Guangdong, China.
Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.; Key Laboratory of Nephrology, National Health Commission (NHC) and Guangdong Province, Guangzhou, Guangdong, China.; Guangdong Medical University, Zhanjiang, Guangdong, China..
Semin Nephrol. 2018 Sep;38(5):455-460. doi: 10.1016/j.semnephrol.2018.05.015.
IgA nephropathy (IgAN) is one of the most common primary glomerulonephritides throughout the world and a major cause of end-stage renal disease among the East Asian population. It is widely considered that genetic factors play an important role in the pathogenesis of IgAN. This article summarizes the recent achievements in the genetic studies of IgAN, focusing mainly on studies performed in East Asia, from the early association studies of candidate genes and family based designs, to the recent genome-wide association studies. There have been five large genome-wide association studies performed that have identified multiple susceptibility loci for IgAN, especially some novel loci identified in the Chinese population. Genes within these loci have provided important insights into the potential biological mechanisms and pathways that influence genetic risk to IgAN. In susceptibility loci/genes, the study of genetic interaction and structural variants (such as copy number variation) was conducted to identify more variants associated with IgAN and disease progression. Genetic studies of IgAN from East Asia have made great achievements over the years. Most susceptibility loci discovered to date encode genes involved in the response to mucosal pathogens, suggesting that an intestinal-immune network for IgA production may be involved in the pathogenesis of IgAN. Although genetic studies of the complex diseases are challenging, for future genetic studies in IgAN, new genetic techniques and methods of analysis, especially next-generation sequencing, need to be applied to push the genetic studies forward.
IgA 肾病 (IgAN) 是全世界最常见的原发性肾小球肾炎之一，也是东亚人群终末期肾病的主要病因。遗传因素被广泛认为在 IgAN 的发病机制中起重要作用。本文总结了 IgAN 遗传研究的最新进展，主要集中在东亚地区的研究，从早期候选基因的关联研究和基于家系的设计，到最近的全基因组关联研究。已经进行了五项大型全基因组关联研究，确定了 IgAN 的多个易感位点，特别是在中国人群中发现的一些新位点。这些位点内的基因为影响 IgAN 遗传风险的潜在生物学机制和途径提供了重要的见解。在易感位点/基因中，进行了遗传相互作用和结构变异（如拷贝数变异）的研究，以鉴定与 IgAN 和疾病进展相关的更多变异。多年来，东亚地区对 IgAN 的遗传研究取得了巨大成就。迄今为止发现的大多数易感位点编码的基因参与了对粘膜病原体的反应，这表明 IgA 产生的肠道免疫网络可能参与了 IgAN 的发病机制。尽管复杂疾病的遗传研究具有挑战性，但对于未来的 IgAN 遗传研究，需要应用新的遗传技术和分析方法，特别是下一代测序，以推动遗传研究的进展。
