| Common variation in GPC5 is associated with acquired nephrotic syndrome. | |
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MedLine Citation:
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PMID: 21441931 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 × 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. |
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Authors:
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Koji Okamoto; Katsushi Tokunaga; Kent Doi; Toshiro Fujita; Hodaka Suzuki; Tetsuo Katoh; Tsuyoshi Watanabe; Nao Nishida; Akihiko Mabuchi; Atsushi Takahashi; Michiaki Kubo; Shiro Maeda; Yusuke Nakamura; Eisei Noiri |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-27 |
Journal Detail:
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Title: Nature genetics Volume: - ISSN: 1546-1718 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9216904 Medline TA: Nat Genet Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Department of Nephrology and Endocrinology, Department of Hemodialysis and Apheresis, University Hospital, The University of Tokyo, Tokyo, Japan. [2] Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. |
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