Interaction between the alpha-T catenin gene (VR22) and APOE in Alzheimer's disease.

TitleInteraction between the alpha-T catenin gene (VR22) and APOE in Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2005
AuthorsMartin ER, Bronson PG, Li Y-J, Wall N, Chung R-H, Schmechel DE, Small G, Xu P-T, Bartlett J, Schnetz-Boutaud N, Haines JL, Gilbert JR, Pericak-Vance MA
JournalJ Med Genet
Volume42
Issue10
Pagination787-92
Date Published2005 Oct
ISSN1468-6244
KeywordsAged, Aged, 80 and over, alpha Catenin, Alzheimer Disease, Apolipoproteins E, Female, Genetic Predisposition to Disease, Humans, Linkage Disequilibrium, Male, Polymorphism, Genetic, Polymorphism, Single Nucleotide
Abstract

BACKGROUND: APOE is the only gene that has been consistently replicated as a risk factor for late onset Alzheimer's disease. Several recent studies have identified linkage to chromosome 10 for both risk and age of onset, suggesting that this region harbours genes that influence the development of the disease. A recent study reported association between single nucleotide polymorphisms (SNPs) in the VR22 gene (CTNNA3) on chromosome 10 and plasma levels of Abeta42, an endophenotype related to Alzheimer's disease.

OBJECTIVE: To assess whether polymorphisms in the VR22 gene are associated with Alzheimer's disease in a large sample of Alzheimer's disease families and an independent set of unrelated cases and controls.

RESULTS: Several SNPs showed association in either the family based or case-control analyses (p<0.05). The most consistent findings were with SNP6, for which there was significant evidence of association in both the families and the unrelated cases and controls. Furthermore, there was evidence of significant interaction between APOE-4 and two of the VR22 SNPs, with the strongest evidence of association being concentrated in individuals carrying APOE-4.

CONCLUSIONS: This study suggests that VR22 or a nearby gene influences susceptibility to Alzheimer's disease, and the effect is dependent on APOE status.

DOI10.1136/jmg.2004.029553
Alternate JournalJ. Med. Genet.
PubMed ID16199552
PubMed Central IDPMC1735932
Grant ListR01 AG19757 / AG / NIA NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
R01 NS31153 / NS / NINDS NIH HHS / United States
R01 AG021547 / AG / NIA NIH HHS / United States
RR 00095 / RR / NCRR NIH HHS / United States
R01 AG20135 / AG / NIA NIH HHS / United States