Linked Life Data

21731745

Source:http://linkedlifedata.com/resource/pubmed/id/21731745

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-7-6
pubmed:abstractText
The insulin degrading enzyme (IDE) variant, v311 (rs6583817), is associated with increased post-mortem cerebellar IDE mRNA, decreased plasma ?-amyloid (A?), decreased risk for Alzheimer's disease (AD) and increased reporter gene expression, suggesting that it is a functional variant driving increased IDE expression. To identify other functional IDE variants, we have tested v685, rs11187061 (associated with decreased cerebellar IDE mRNA) and variants on H6, the haplotype tagged by v311 (v10; rs4646958, v315; rs7895832, v687; rs17107734 and v154; rs4646957), for altered in vitro reporter gene expression. The reporter gene expression levels associated with the second most common haplotype (H2) successfully replicated the post-mortem findings in hepatocytoma (0.89 fold-change, p?=?0.04) but not neuroblastoma cells. Successful in vitro replication was achieved for H6 in neuroblastoma cells when the sequence was cloned 5' to the promoter (1.18 fold-change, p?=?0.006) and 3' to the reporter gene (1.29 fold change, p?=?0.003), an effect contributed to by four variants (v10, v315, v154 and v311). Since IDE mediates A? degradation, variants that regulate IDE expression could represent good therapeutic targets for AD.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1932-6203
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
e21429
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Multiple insulin degrading enzyme variants alter in vitro reporter gene expression.
pubmed:affiliation
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, United States of America.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural