IGA分子遗传学进展剖析.doc

IgA肾病分子遗传学研究新进展 Advances in molecular genetics research of IgA nephropathy Abstract: IgA nephropathy (IgAN), which can develop into end-stage renal disease, is the most common primary glomerulonephritis. The pathogenesis of IgAN is not clear, many studies have confirmed that genetic susceptibility is associated with IgAN, and it belongs to polygenic disease. Some studies have found that IgAN was associated with chromosome 6q22-23, 2q36 by linkage analysis, and several candidate genes were confirmed by association study to be associated with IgAN, such as ACE、FCAR、HLA. In recent years, as the progression of molecular genetics and the Human Genome Project, more attention was paid to the role of genetic factors in the pathogenesis of IgAN. In this paper, the latest progress of molecular genetics research of IgAN will be reviewed. Key words: IgA nephropathy(IgAN); pathogenesis; linkage analysis; candidate gene; genome-wide association study(GWAS) 原发性IgA肾病(IgA nephropathy, IgAN)首先是由Berge在1968年报道的,以肾小球系膜区IgA或IgA免疫复合物沉积为主要病理特征。目前认为与感染、炎症介质、免疫反应、遗传等因素有关。越来越多的证据表明不同地域、不同种族IgAN具有明显不同的发病率，并且具有家族聚集性，提示遗传因素在IgAN的发病机制中有重要影响。目前对于IgAN的遗传学研究主要为以IgAN家系为研究对象的连锁分析研究和以散发性IgAN为研究对象的相关性研究。 1　连锁分析(Linkage analysis) 2.1　候选基因关联研究(candidate gene association study) 2.1.1　选择素(selectin)基因 2.1.2　转化生长因子β1(TGFβ1)基因 2.1.3　T细胞受体基因(TRAC) 2.1.4　血管紧张素转换酶和糜蛋白酶基因(ACE,CMA) 2.1.5　Fcα受体基因(FCAR) 2.1.6　其它 2.2.1　聚合免疫球蛋白受体基因(PIGR) 2.2.2　免疫球蛋白μ-结合蛋白2基因(IGHMBP2) 2.2.3　人类白细胞抗原基因(HLA) [3] 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]. J Am Soc Nephrol, 2007, 18(8): 2408–2415. [4] Takei T, Iida A, Nitta K, et al. Association between single-nucleotide polymorphisms in selectin genes and immunoglobulin a nephropathy[J]. Am J Hum Genet, 2002, 70(3): 781–786. [5] Park SR, Lee JH, Kim PH. Smad3 and Smad4 mediate transforming growth factor-beta1-induced IgA expression in murine B lymphocytes[J]. Eur J Immunol