Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Lack of association between UBQLN1 and Alzheimer disease

Lack of association between UBQLN1 and Alzheimer disease Alzheimer disease (AD) is heterogeneous and complex with a strong genetic diathesis. It is the most common cause of dementia affecting the elderly. Linkage studies (Kehoe et al., 1999; Hum Mol Genet 8: 237–245); (Pericak‐Vance et al., 2000; Exp Gerontol 35: 1343–1352); (Myers et al., 2002; Am J Med Genet 114: 235–244); (Blacker et al., 2003; Hum Mol Genet 12: 23–32) identified chromosome 9q as a region containing a possible AD candidate gene. Functional protein studies (Mah et al., 2000; J Cell Biol 151: 847–862); (Ko et al., 2002; J Biol Chem 277: 35386–35392) identified the UBQLN1 gene on chromosome 9q that encodes ubiquilin as a likely candidate for a role in late‐onset AD pathogenesis. A recent family‐based study by (Bertram et al., 2005; N Engl J 352: 884–894) reported genetic association and expression evidence for a putative AD risk allele of an intronic single nucleotide polymorphism (SNP) within the UBQLN1 gene. In this study, we comprehensively assessed whether any of seven polymorphisms located across the UBQLN1 gene are associated with AD in another large family‐based data set and an independent case‐control data set. We found no significant association of AD risk with any of the seven SNPs genotyped (including those SNPs previously reported by Bertram et al.) in either the family‐based or case‐control data set. Age‐specific analyses and analyses conditional on Apolipoprotein E (ApoE) genotype and sex also revealed no significant associations to AD risk in either data set. Using age at onset (AAO) as a quantitative trait revealed a modest age modifying association; however, the results were inconsistent between the data sets. Our results suggest that UBQLN1 variants do not increase risk for AD in these data. © 2006 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Medical Genetics part B Wiley

Lack of association between UBQLN1 and Alzheimer disease

Download PDF
6 pages

Loading next page...
 
/lp/wiley/lack-of-association-between-ubqln1-and-alzheimer-disease-7TUYwLa1R3

References (42)

Publisher
Wiley
Copyright
Copyright © 2006 Wiley‐Liss, Inc., A Wiley Company
ISSN
1552-4841
eISSN
1552-485X
DOI
10.1002/ajmg.b.30298
pmid
16526030
Publisher site
See Article on Publisher Site

Abstract

Alzheimer disease (AD) is heterogeneous and complex with a strong genetic diathesis. It is the most common cause of dementia affecting the elderly. Linkage studies (Kehoe et al., 1999; Hum Mol Genet 8: 237–245); (Pericak‐Vance et al., 2000; Exp Gerontol 35: 1343–1352); (Myers et al., 2002; Am J Med Genet 114: 235–244); (Blacker et al., 2003; Hum Mol Genet 12: 23–32) identified chromosome 9q as a region containing a possible AD candidate gene. Functional protein studies (Mah et al., 2000; J Cell Biol 151: 847–862); (Ko et al., 2002; J Biol Chem 277: 35386–35392) identified the UBQLN1 gene on chromosome 9q that encodes ubiquilin as a likely candidate for a role in late‐onset AD pathogenesis. A recent family‐based study by (Bertram et al., 2005; N Engl J 352: 884–894) reported genetic association and expression evidence for a putative AD risk allele of an intronic single nucleotide polymorphism (SNP) within the UBQLN1 gene. In this study, we comprehensively assessed whether any of seven polymorphisms located across the UBQLN1 gene are associated with AD in another large family‐based data set and an independent case‐control data set. We found no significant association of AD risk with any of the seven SNPs genotyped (including those SNPs previously reported by Bertram et al.) in either the family‐based or case‐control data set. Age‐specific analyses and analyses conditional on Apolipoprotein E (ApoE) genotype and sex also revealed no significant associations to AD risk in either data set. Using age at onset (AAO) as a quantitative trait revealed a modest age modifying association; however, the results were inconsistent between the data sets. Our results suggest that UBQLN1 variants do not increase risk for AD in these data. © 2006 Wiley‐Liss, Inc.

Journal

American Journal of Medical Genetics part B – Wiley

Published: Apr 5, 2006

Keywords: ubiquilin; ubiquitin; dementia; association; quantitative trait

There are no references for this article.