| Popis: |
IgA nephropathy is the most common form of primary glomerulonephritis, with a variable prevalence depending on the geographic area of examination. Marked differences in disease prevalence has suggested that genetics could play a role in the pathogenesis of the disease, indicating the existence of susceptibility genes detected with different frequencies in geographically separated populations. Moreover, familial forms of IgAN have been reported worldwide, in sibling pairs, families and extended pedigrees belonging to geographically isolated populations. In this article we describe recent discoveries in genetic studies on IgAN. If candidate-gene association studies require first survey on the pathogenesis of the disease, since the candidate loci are selected on the basis of information gathered from traditional biology, the linkage analysis consist in an alternative approach. Several susceptibility loci have been identified in pedigrees segregating for IgAN, but not the causative mutations of the disease. Further progress in the field of knowledge about the genetics of IgAN has recently been obtained by the application of genome-wide association studies (GWAS) in large cohorts of cases and controls of IgAN. GWAS have identified multiple susceptibility loci coding for genes involved in critical mechanisms for the development of IgAN and, accordingly, have shed new light on the biology of the disease, revealing unknown pathogenic pathways. The close connection between IgAN and many autoimmune diseases has been demonstrated. Moreover, these studies have made the correlation of genetic risk score of developing IgAN with the geo-epidemiological aspect of the disease possible. The goal of the integrated genomic approach will be to discover new potential therapeutic targets. |
