NEW YORK (Reuters Health) - Variants in the gene for ubiquilin 1 (UBQLN1) on chromosome 9q22 appear to markedly increase the risk of Alzheimer’s disease, according to a report in The New England Journal of Medicine for March 3.
At present, more than 160 mutations in four genes have been linked to Alzheimer’s disease, and yet together they are thought to account for less than half the genetic variance seen, the authors explain. Thus, there are probably additional Alzheimer’s susceptibility genes.
Previous reports have linked regions on chromosome 9 with the disease. However, the locus or loci responsible for the association have not been fully characterized.
In the present study, Dr. Rudolph E. Tanzi, from the MassGeneral Institute for Neurodegenerative Disease in Charlestown, Massachusetts, and colleagues tested 437 families with Alzheimer’s disease (1439 subjects) for 19 variants in three genes on chromosome 9.
The variants that showed a link to Alzheimer’s disease were then tested for in an independent group of 217 sibships discordant for the disease (489 subjects).
As noted, several variants in the UBQLN1 gene were associated with Alzheimer’s disease, a finding that was confirmed in the sibship analysis.
A functional analysis of implicated variants was carried out using brain tissue from Alzheimer’s patients and control subjects, and this showed that the variants seemed to result in an alternatively spliced form of UBQLN1.
“Additional genetic studies involving both family-based and large case-control samples, along with more extensive functional testing of UBLQN1, will be required to characterize the potential effect of this gene on the risk of Alzheimer’s disease,” the researchers conclude.
Source: N Engl J Med 2005;325:884-894. [ Google search on this article ]
MeSH Headings:Cognition Disorders: Gene DeletionCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
