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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2011-4-27
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pubmed: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 × 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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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1546-1718
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pubmed:author |
pubmed-author:FujitaToshiroT,
pubmed-author:KatohTetsuoT,
pubmed-author:KiemD TDT,
pubmed-author:KuboMichiakiM,
pubmed-author:MabuchiAkihikoA,
pubmed-author:MaedaShiroS,
pubmed-author:NakamuraYusukeY,
pubmed-author:NishidaNaoN,
pubmed-author:NoiriEiseiE,
pubmed-author:OkamotoKojiK,
pubmed-author:SuzukiHodakaH,
pubmed-author:TakahashiAtsushiA,
pubmed-author:TokunagaKatsushiK,
pubmed-author:WatanabeTsuyoshiT
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pubmed:issnType |
Electronic
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
459-63
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pubmed:meshHeading |
pubmed-meshheading:21441931-Adult,
pubmed-meshheading:21441931-Aged,
pubmed-meshheading:21441931-Animals,
pubmed-meshheading:21441931-Base Sequence,
pubmed-meshheading:21441931-Case-Control Studies,
pubmed-meshheading:21441931-DNA Primers,
pubmed-meshheading:21441931-Disease Models, Animal,
pubmed-meshheading:21441931-Female,
pubmed-meshheading:21441931-Gene Knockdown Techniques,
pubmed-meshheading:21441931-Genome-Wide Association Study,
pubmed-meshheading:21441931-Glypicans,
pubmed-meshheading:21441931-Humans,
pubmed-meshheading:21441931-Male,
pubmed-meshheading:21441931-Mice,
pubmed-meshheading:21441931-Middle Aged,
pubmed-meshheading:21441931-Models, Genetic,
pubmed-meshheading:21441931-Nephrotic Syndrome,
pubmed-meshheading:21441931-Podocytes,
pubmed-meshheading:21441931-Polymorphism, Single Nucleotide,
pubmed-meshheading:21441931-RNA, Messenger,
pubmed-meshheading:21441931-RNA, Small Interfering
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pubmed:year |
2011
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pubmed:articleTitle |
Common variation in GPC5 is associated with acquired nephrotic syndrome.
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pubmed:affiliation |
Department of Nephrology and Endocrinology, University Hospital, The University of Tokyo, Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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