IgAN 是全球范围内最常见的肾小球肾炎形式。 在亚洲进行的所有肾脏活检中诊断为 IgAN 的比例为 40%,在欧洲所有肾脏活检中为 20%,在美国所有肾脏活检中为 10%。[10]Galla JH. IgA nephropathy. Kidney Int. 1995 Feb;47(2):377-87.http://www.ncbi.nlm.nih.gov/pubmed/7723227?tool=bestpractice.com[11]Haas M. Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis. 1997 Jun;29(6):829-42.http://www.ncbi.nlm.nih.gov/pubmed/9186068?tool=bestpractice.com[12]Iseki K, Miyasoto F, Uehara H, et al. Outcome study of renal biopsy patients in Okinawa, Japan. Kidney Int. 2004 Sep;66(3):914-9.http://www.ncbi.nlm.nih.gov/pubmed/15327381?tool=bestpractice.com[13]Li LS, Liu ZH. Epidemiologic data of renal diseases from a single unit in China: analysis based on 13,519 renal biopsies. Kidney Int. 2004 Sep;66(3):920-3.http://www.ncbi.nlm.nih.gov/pubmed/15327382?tool=bestpractice.com[14]Suzuki K, Honda K, Tanabe K, et al. Incidence of latent mesangial IgA deposition in renal allograft donors in Japan. Kidney Int. 2003 Jun;63(6):2286-94.http://www.ncbi.nlm.nih.gov/pubmed/12753320?tool=bestpractice.com[15]Waldherr R, Rambausek M, Duncker D, et al. Frequency of mesangial IgA deposits in a non-selected autopsy series. Nephrol Dial Transplant. 1989;4(11):943-6.http://www.ncbi.nlm.nih.gov/pubmed/2516884?tool=bestpractice.com 这些比例可能不同,其原因至少部分来自于公共卫生筛查和活检实践的差异。 在有肾脏病主动筛查计划的国家和实施肾脏活检门槛低的中心,报告的 IgAN 发病率高,发现的轻度疾病患者也更多。
从北美到亚洲,此病的发病率和当前掌握的遗传风险等位基因分布存在着明确的从西到东增高的趋势。 但特定等位基因的准确作用仍不明确。
在 4 个广泛发表的家族性 IgAN 家系中,各家系的遗传学连锁存在差异。[16]Gharavi AG, Yan Y, Scolari F, et al. IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23. Nat Genet. 2000 Nov;26(3):354-7.http://www.ncbi.nlm.nih.gov/pubmed/11062479?tool=bestpractice.com[17]Bisceglia L, Cerullo G, Forabosco P, et al. Genetic heterogeneity in Italian families with IgA nephropathy: suggestive linkage for two novel IgA nephropathy loci. Am J Hum Genet. 2006 Dec;79(6):1130-4.http://www.cell.com/ajhg/fulltext/S0002-9297(07)63477-6http://www.ncbi.nlm.nih.gov/pubmed/17186473?tool=bestpractice.com[18]Paterson AD, Liu XQ, Wang K, et al. Genome-wide linkage scan of a large family with IgA nephropathy localizes a novel susceptibility locus to chromosome 2q36. J Am Soc Nephrol. 2007 Aug;18(8):2408-15.http://jasn.asnjournals.org/content/18/8/2408.longhttp://www.ncbi.nlm.nih.gov/pubmed/17634434?tool=bestpractice.com[19]Karnib HH, Sanna-Cherchi S, Zalloua PA, et al. Characterization of a large Lebanese family segregating IgA nephropathy. Nephrol Dial Transplant. 2007 Mar;22(3):772-7.https://academic.oup.com/ndt/article/22/3/772/1899254http://www.ncbi.nlm.nih.gov/pubmed/17172253?tool=bestpractice.com 对 3 个新基因位点(命名为 IGAN1、IGAN2、IGAN3)进行的研究未发现任何可能的候选基因。 在加拿大系谱中发现的 2q36 基因位点可能提供信息,因为它包含编码基底膜胶原的 COL4A3 和 COL4A4 基因,而这些基因的突变与薄基底膜肾病有关。[20]Deltas C, Pierides A, Voskarides K. Molecular genetics of familial hematuric diseases. Nephrol Dial Transplant. 2013 Dec;28(12):2946-60.https://academic.oup.com/ndt/article/28/12/2946/1832199http://www.ncbi.nlm.nih.gov/pubmed/24046192?tool=bestpractice.com 4 项 IgAN 全基因组关联研究 (GWAS) 的结果显示,自体免疫或炎症特征与单核苷酸多态性 (SNP) 的丰富程度相关(染色体 6p21 和染色体 1q32 HLA 区域内存在多个等位基因,提示补体调节蛋白发挥作用)。[21]Kiryluk K, Li Y, Sanna-Cherchi S, et al. Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis. PLoS Genet. 2012;8(6):e1002765.http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002765http://www.ncbi.nlm.nih.gov/pubmed/22737082?tool=bestpractice.com[22]Gharavi AG, Kiryluk K, Choi M, et al. Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nat Genet. 2011 Mar 13;43(4):321-7.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412515/http://www.ncbi.nlm.nih.gov/pubmed/21399633?tool=bestpractice.com[23]Feehally J, Farrall M, Boland A, et al. HLA has strongest association with IgA nephropathy in genome-wide analysis. J Am Soc Nephrol. 2010 Oct;21(10):1791-7.http://jasn.asnjournals.org/content/21/10/1791.longhttp://www.ncbi.nlm.nih.gov/pubmed/20595679?tool=bestpractice.com[24]Kiryluk K, Li Y, Scolari F, et al. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat Genet. 2014 Nov;46(11):1187-96.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213311/http://www.ncbi.nlm.nih.gov/pubmed/25305756?tool=bestpractice.com 另外,很多与 IgAN 相关的基因位点可编码蛋白,这些蛋白参与维持肠道屏障、调节对病原体的黏膜免疫反应。