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Comment
. 2007 Jan;44(1):e63.
doi: 10.1136/jmg.2005.039263.

Is alpha-T catenin (VR22) an Alzheimer's disease risk gene?

Lars Bertram, Kristina Mullin, Michele Parkinson, Monica Hsiao, Thomas J Moscarillo, Steven L Wagner, K David Becker, Gonul Velicelebi, Deborah Blacker, Rudolph E Tanzi
Comment

Is alpha-T catenin (VR22) an Alzheimer's disease risk gene?

Lars Bertram et al. J Med Genet. 2007 Jan.

Abstract

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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Conflict of interest statement

Competing interests: None declared.

Comment on

References

    1. Martin E R, Bronson P G, Li Y J, Wall N, Chung R H, Schmechel D E, Small G, Xu P T, Bartlett J, Schnetz‐Boutaud N, Haines J L, Gilbert J R, Pericak‐Vance M A. Interaction between the alpha‐T catenin gene (VR22) and APOE in Alzheimer's disease. J Med Genet 200542787–792. - PMC - PubMed
    1. Blomqvist M E, Andreasen N, Bogdanovic N, Blennow K, Brookes A J, Prince J A. Genetic variation in CTNNA3 encoding alpha‐3 catenin and Alzheimer's disease. Neurosci Lett 2004358220–222. - PubMed
    1. Busby V, Goossens S, Nowotny P, Hamilton G, Smemo S, Harold D, Turic D, Jehu L, Myers A, Womick M, Woo D, Compton D, Doil L M, Tacey K M, Lau K F, Al‐Saraj S, Killick R, Pickering‐Brown S, Moore P, Hollingworth P, Archer N, Foy C, Walter S, Lendon C, Iwatsubo T, Morris J C, Norton J, Mann D, Janssens B, Hardy J, O'Donovan M, Jones L, Williams J, Holmans P, Owen M J, Grupe A, Powell J, van Hengel J, Goate A, Van Roy F, Lovestone S. Alpha‐T‐catenin is expressed in human brain and interacts with the Wnt signaling pathway but is not responsible for linkage to chromosome 10 in Alzheimer's disease. Neuromolecular Med 20045133–146. - PubMed
    1. Cellini E, Bagnoli S, Tedde A, Nacmias B, Piacentini S, Sorbi S. Insulin degrading enzyme and alpha‐3 catenin polymorphisms in Italian patients with Alzheimer disease. Alzheimer Dis Assoc Disord 200519246–247. - PubMed
    1. Ertekin‐Taner N, Ronald J, Asahara H, Younkin L, Hella M, Jain S, Gnida E, Younkin S, Fadale D, Ohyagi Y, Singleton A, Scanlin L, de Andrade M, Petersen R, Graff‐Radford N, Hutton M. Fine mapping of the alpha‐T catenin gene to a quantitative trait locus on chromosome 10 in late‐onset Alzheimer's disease pedigrees. Hum Mol Genet 2003123133–3143. - PMC - PubMed