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PLoS One. 2011;6(10):e24588. doi: 10.1371/journal.pone.0024588. Epub 2011 Oct 26.

Impact of genetic variation in SORCS1 on memory retention.

Author information

1
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.

Abstract

OBJECTIVE:

We previously reported that genetic variants in SORCS1 increase the risk of AD, that over-expression of SorCS1 reduces γ-secretase activity and Aβ levels, and that SorCS1 suppression increases γ-secretase processing of APP and Aβ levels. We now explored the effect of variation in SORCS1 on memory.

METHODS:

We explored associations between SORCS1-SNPs and memory retention in the NIA-LOAD case control dataset (162 cases,670 controls) and a cohort of Caribbean Hispanics (549 cases,544 controls) using single marker and haplotype analyses.

RESULTS:

Three SNPs in intron 1, were associated with memory retention in the NIA-LOAD dataset or the Caribbean Hispanic dataset (rs10884402(A allele:β = -0.15,p = 0.008), rs7078098(C allele:β = 0.18,p = 0.007) and rs950809(C allele:β = 0.17,p = 0.008)) and all three SNPs were significant in a meta-analysis of both datasets (0.002<p<0.03). The corresponding A-T-T haplotype for these SNPs was associated with lower scores in both datasets (p = 0.02,p = 0.0009), and the complementary G-C-C haplotype was associated with higher scores in NIA-LOAD (p = 0.02). These associations were restricted to cases.

CONCLUSIONS:

Variation in intron 1 in SORCS1 is associated with memory changes in AD.

PMID:
22046233
PMCID:
PMC3202519
DOI:
10.1371/journal.pone.0024588
[Indexed for MEDLINE]
Free PMC Article

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