| Is alpha-T catenin (VR22) an Alzheimer's disease risk gene? | |
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MedLine Citation:
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PMID: 17209133 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Recently, conflicting reports have been published on the potential role of genetic variants in the alpha-T catenin gene (VR22; CTNNA3) on the risk for Alzheimer's disease. In these papers, evidence for association is mostly observed in multiplex families with Alzheimer's disease, whereas case-control samples of sporadic Alzheimer's disease are predominantly negative. METHODS: After sequencing VR22 in multiplex families with Alzheimer's disease linked to chromosome 10q21, we identified a novel non-synonymous (Ser596Asn; rs4548513) single nucleotide polymorphism (SNP). This and four non-coding SNPs were assessed in two independent samples of families with Alzheimer's disease, one with 1439 subjects from 437 multiplex families with Alzheimer's disease and the other with 489 subjects from 217 discordant sibships. RESULTS: A weak association with the Ser596Asn SNP in the multiplex sample, predominantly in families with late-onset Alzheimer's disease (p = 0.02), was observed. However, this association does not seem to contribute substantially to the chromosome 10 Alzheimer's disease linkage signal that we and others have reported previously. No evidence was found of association with any of the four additional SNPs tested in the multiplex families with Alzheimer's disease. Finally, the Ser596Asn change was not associated with the risk for Alzheimer's disease in the independent discordant sibship sample. CONCLUSIONS: This is the first study to report evidence of an association between a potentially functional, non-synonymous SNP in VR22 and the risk for Alzheimer's disease. As the underlying effects are probably small, and are only seen in families with multiple affected members, the population-wide significance of this finding remains to be determined. |
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Authors:
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Lars Bertram; Kristina Mullin; Michele Parkinson; Monica Hsiao; Thomas J Moscarillo; Steven L Wagner; K David Becker; Gonul Velicelebi; Deborah Blacker; Rudolph E Tanzi |
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Publication Detail:
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Type: Comment; Letter; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of medical genetics Volume: 44 ISSN: 1468-6244 ISO Abbreviation: J. Med. Genet. Publication Date: 2007 Jan |
Date Detail:
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Created Date: 2007-01-08 Completed Date: 2007-01-30 Revised Date: 2010-09-15 |
Medline Journal Info:
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Nlm Unique ID: 2985087R Medline TA: J Med Genet Country: England |
Other Details:
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Languages: eng Pagination: e63 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alzheimer Disease
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genetics* Amino Acid Substitution Family Genetic Predisposition to Disease* Humans Linkage Disequilibrium Polymorphism, Single Nucleotide Risk Factors alpha Catenin / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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1R01 AG023667-01/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/alpha Catenin |
| Comments/Corrections | |
Comment On:
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J Med Genet. 2005 Oct;42(10):787-92
[PMID:
16199552
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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