| First Author | Okamoto K | Year | 2011 |
| Journal | Nat Genet | Volume | 43 |
| Issue | 5 | Pages | 459-63 |
| PubMed ID | 21441931 | Mgi Jnum | J:172070 |
| Mgi Id | MGI:5003391 | Doi | 10.1038/ng.792 |
| Citation | Okamoto K, et al. (2011) Common variation in GPC5 is associated with acquired nephrotic syndrome. Nat Genet 43(5):459-63 |
| abstractText | Severe proteinuria is a defining factor of nephrotic syndrome irrespective of the etiology. Investigation of congenital nephrotic syndrome has shown that dysfunction of glomerular epithelial cells (podocytes) plays a crucial role in this disease. Acquired nephrotic syndrome is also assumed to be associated with podocyte injury. Here we identify an association between variants in GPC5, encoding glypican-5, and acquired nephrotic syndrome through a genome-wide association study and replication analysis (P value under a recessive model (P(rec)) = 6.0 x 10(-11), odds ratio = 2.54). We show that GPC5 is expressed in podocytes and that the risk genotype is associated with higher expression. We further show that podocyte-specific knockdown and systemic short interfering RNA injection confers resistance to podocyte injury in mouse models of nephrosis. This study identifies GPC5 as a new susceptibility gene for nephrotic syndrome and implicates GPC5 as a promising therapeutic target for reducing podocyte vulnerability in glomerular disease. |
