Common variation in GPC5 is associated with acquired nephrotic syndrome

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

研究成果: Article

58 引用 (Scopus)

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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.

元の言語English
ページ(範囲)459-465
ページ数7
ジャーナルNature Genetics
43
発行部数5
DOI
出版物ステータスPublished - 01-05-2011

All Science Journal Classification (ASJC) codes

  • Genetics

フィンガープリント Common variation in GPC5 is associated with acquired nephrotic syndrome' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    Okamoto, K., Tokunaga, K., Doi, K., Fujita, T., Suzuki, H., Katoh, T., Watanabe, T., Nishida, N., Mabuchi, A., Takahashi, A., Kubo, M., Maeda, S., Nakamura, Y., & Noiri, E. (2011). Common variation in GPC5 is associated with acquired nephrotic syndrome. Nature Genetics, 43(5), 459-465. https://doi.org/10.1038/ng.792