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原发性IgA肾病(IgA nephropathy,IgAN)是最常见的肾小球肾炎,家族聚集起病及发病率的人种差异均提示遗传因素为重要致病机制之一。尽管迄今为止仍未找到明确的致病基因,但随着遗传学研究方法的改进,特别是高密度基因芯片的出现及广泛应用以及人类基因组计划(HGP)的推进,在该领域出现了许多振奋人心的研究成果。连锁分析对家族性IgA肾病基因定位至少已得到4个易感区段;关联分析提示IgAN发病可能与IgA1糖基化过程中的关键酶相关;基因表达谱研究通过对外周血白细胞和肾组织的表达谱分析,发现了一系列与IgAN起病与进展潜在相关的基因;借助IgAN动物模型,则有助于明确候选基因功能和阐明致病机制。近年来全基因组关联研究(GWAS)成为遗传学研究的热点,该方法应用高密度基因芯片,无需假设易感基因,定位微效及中效易感基因效能要强于连锁分析,最近已有2项IgAN的GWAS研究结果发表。复杂性疾病的基因定位极具挑战性,但随着遗传学研究方法的不断改进以及新技术的出现,特别是下一代测序方法的不断完善,必将加快推动IgAN致病基因定位工作。
Primary IgA nephropathy (IgAN) is the most common glomerulonephritis. The racial differences in the incidence and incidence of familial aggregation suggest that genetic factors are one of the important pathogenic mechanisms. Although no clear virulence gene has been found so far, there has been a lot of excitement in the field with the development of genetic research methods, especially the emergence and widespread use of high-density gene chips and the advancement of the Human Genome Project (HGP) People’s research results. Linkage analysis of familial IgA nephropathy gene loci has been at least four susceptible segments; association analysis suggests IgAN pathogenesis may be related to IgA1 glycosylation process of key enzymes; gene expression profiling by peripheral blood leukocytes and renal tissue Expression profiling revealed a series of genes potentially associated with the onset and progression of IgAN. With IgAN animal models, it is helpful to clarify the function of candidate genes and elucidate the pathogenesis. In recent years, genome-wide association study (GWAS) has become a hotspot in genetics research. Using high-density microarray, this method does not need to assume susceptible genes, and locus and micro-effect genes are more powerful than linkage analysis. Two recent IgAN GWAS study published. Genetically locating complex diseases is challenging, but with the continuous improvement of genetic research methods and the advent of new technologies, especially the continuous improvement of next-generation sequencing methods, it is bound to accelerate the positioning of IgAN pathogenic genes.