Li Ming, Yu Xueqing
Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, China.
Nephrology (Carlton). 2018 Oct;23 Suppl 4:26-31. doi: 10.1111/nep.13470.
Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulonephritis throughout the world and a major cause of end-stage renal disease among East Asian population. It is widely considered that genetic factors play an important role in the pathogenesis of IgAN. The genetic studies of IgAN, is from the association studies of candidate genes and family-based designs, to the genome-wide association studies. Altogether there are five large genome-wide association studies performed, which have identified multiple susceptibility loci for IgAN, including several novel loci found in Chinese population. The discovery of these susceptibility loci has provided important insight into the potential biological mechanisms and pathways that influence genetic risk to IgAN. In addition, genetic interaction and structural variation (such as copy number variation) studies were also conducted to identify more variants associated with IgAN and disease progression. The genetic studies of IgAN have made great achievements in recent years. Most of susceptibility loci discovered up to date contain genes involved in the response to mucosal pathogens, suggesting that intestinal immune network for IgA production may be involved in the pathogenesis of IgAN. While the genetic studies of the complex diseases remain to be challenging, new genetic and analytical techniques and methods, especially next-generation sequencing-based studies, need to be applied to advance the genetic studies of IgAN. More importantly, we need to identify the genetic factors which influence the clinical phenotypes and renal progression to end-stage renal disease. This will require the integration of genomic data with other omics profiles (e.g. transcriptomics, metabolomics and immunomics) in patients with long-term clinical follow-up data to better understand the factors underlying inter-individual variability, not only in disease susceptibility, but also in the long-term prognosis and healthcare requirements.
免疫球蛋白A肾病（IgAN）是全球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。人们普遍认为遗传因素在IgAN的发病机制中起重要作用。IgAN的遗传学研究，从候选基因的关联研究和基于家系的设计，发展到全基因组关联研究。总共进行了五项大型全基因组关联研究，这些研究已经确定了多个IgAN的易感位点，包括在中国人群中发现的几个新位点。这些易感位点的发现为影响IgAN遗传风险的潜在生物学机制和途径提供了重要见解。此外，还进行了基因相互作用和结构变异（如拷贝数变异）研究，以确定更多与IgAN和疾病进展相关的变异。近年来，IgAN的遗传学研究取得了巨大成就。迄今为止发现的大多数易感位点都包含参与对黏膜病原体反应的基因，这表明肠道IgA产生免疫网络可能参与了IgAN的发病机制。虽然复杂疾病的遗传学研究仍然具有挑战性，但需要应用新的遗传和分析技术及方法，特别是基于新一代测序的研究，来推进IgAN的遗传学研究。更重要的是，我们需要确定影响临床表型和终末期肾病肾脏进展的遗传因素。这将需要将基因组数据与具有长期临床随访数据的患者的其他组学特征（如转录组学、代谢组学和免疫组学）相结合，以更好地了解个体间变异性的潜在因素，不仅包括疾病易感性，还包括长期预后和医疗保健需求。
