中国汉族人群IgA肾病易感基因的精细定位

IgA肾病(IgAN)是临床最常见的原发性肾小球疾病，已有研究表明遗传因素在IgAN发病机制中起重要作用。我们已经完成的中国汉族IgAN全基因组关联分析研究中，发现了两个中国汉族人群特有的遗传易感位点（17p13和8p23），同时还验证了在欧美研究中发现的两个染色体位点（22q12和MHC区域）。本研究拟在前述研究工作基础上，对以上遗传易感位点进行深入研究和分析，即采用新一代测序方法对上述遗传易感位点进行目标区域的高通量测序，从而进一步得到易感染色体区段的完整遗传学变异图谱，包括常见变异、罕见变异和结构变异；明确和定位与IgAN相关的遗传易感基因，并在大样本人群中进行验证；为将来进一步从事基因功能和信号传导通路等研究，阐明遗传易感基因在IgAN发病机制中的作用奠定坚实的基础；对于明确IgAN的遗传发病机制，进一步探索IgAN特异性治疗方法及干预新靶点，具有重要的科学意义和实用价值。

IgA nephropathy (IgAN) is the most common primary glomerulonephritis among patients undergoing renal biopsy; several lines of evidence support the importance of genetic risk factors to the pathogenesis of IgAN. Our previous GWAS study in Chinese Han population for IgAN have identified associations at chromosome loci 17p13 and 8p23. In addition, we found multiple associations in the MHC region and confirmed a previously reported association at 22q12. In this study, we will do the further study to localize the susceptibility genes associated with IgAN. We use resequencing and genotyping to comprehensively characterize the genetic variants map of the disease-associated chromosomal loci, including common variants, rare variants and structural variants; to discover the susceptibility genes associated with IgAN, and do the replication in the separate population; and analysis the susceptibility genes by gene-ontology and pathway tools, to support the evidence of the genetic polymorphisms can influence the susceptibility to IgAN.