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.
PLoS One. 2011;6(10):e24588. doi: 10.1371/journal.pone.0024588. Epub 2011 Oct 26.
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.
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.
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.
Variation in intron 1 in SORCS1 is associated with memory changes in AD.
我们之前报道过，SORCS1 中的遗传变异会增加 AD 的发病风险，SorCS1 的过表达会降低 γ-分泌酶的活性和 Aβ水平，而 SorCS1 的抑制会增加 APP 的 γ-分泌酶加工和 Aβ水平。我们现在探讨了 SORCS1 变异对记忆的影响。
我们使用单标记和单体型分析，在 NIA-LOAD 病例对照数据集（162 例病例，670 例对照）和加勒比西班牙裔人群（549 例病例，544 例对照）中，探索了 SORCS1-SNPs 与记忆保留之间的关联。
在 NIA-LOAD 数据集或加勒比西班牙裔数据集中，有三个位于内含子 1 中的 SNPs 与记忆保留相关（rs10884402[A 等位基因：β=-0.15，p=0.008]、rs7078098[C 等位基因：β=0.18，p=0.007]和 rs950809[C 等位基因：β=0.17，p=0.008]），并且这三个 SNPs 在两个数据集的荟萃分析中均有显著性（0.002<p<0.03）。这些 SNPs 的相应 A-T-T 单体型与两个数据集的得分降低相关（p=0.02，p=0.0009），而互补的 G-C-C 单体型与 NIA-LOAD 的得分升高相关（p=0.02）。这些关联仅限于病例。
SORCS1 内含子 1 中的变异与 AD 中的记忆变化有关。
