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Impact of genetic variation in SORCS1 on memory retention.

ABSTRACT: OBJECTIVE:We previously reported that genetic variants in SORCS1 increase the risk of AD, that over-expression of SorCS1 reduces ?-secretase activity and A? levels, and that SorCS1 suppression increases ?-secretase processing of APP and A? 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:? = -0.15,p = 0.008), rs7078098(C allele:? = 0.18,p = 0.007) and rs950809(C allele:? = 0.17,p = 0.008)) and all three SNPs were significant in a meta-analysis of both datasets (0.002

SUBMITTER: Reitz C

PROVIDER: S-EPMC3202519 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Impact of genetic variation in SORCS1 on memory retention.

Reitz Christiane C Lee Joseph H JH Rogers Robert S RS Mayeux Richard R

PloS one 20111026 10

<h4>Objective</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 22046233

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Project description:Toll-like receptors (TLRs) are expressed not only in immune cells but also in a variety of tumor cells. Single-nucleotide polymorphisms (SNPs) located in the TLRs' promoter or the 3' untranslated region may affect gene expression by affecting the activity of the promoter or regulating the binding of mRNA to miRNA. This study aimed to investigate the association of the SNPs in TLR genes with the susceptibility to NSCLC. This case-control study involved 700 lung cancer patients and 700 healthy controls. All individuals were genotyped for all selected SNPs in TLR genes using polymerase chain reaction (PCR) test-based restriction fragment length polymorphism (PCR-RFLP) and TaqMan SNP genotyping assay. The association of genetic variations in TLRs with the susceptibility to NSCLC was evaluated by unconditional logistic regression with OR (95% CI). After evaluating transcriptional factor or miRNA binding capability by bioinformatics methods, six TLRs were identified for further analysis. We did not find that TLR3 rs5743303, TLR4 rs1927914, TLR4 rs11536891, TLR5 rs1640816, and TLR7 rs3853839 were associated with NSCLC risk (P > 0.05). Our data showed that TLR4 rs7869402?C?>?T polymorphism reduced the risk of NSCLC with OR (95% CI) of 0.63 (0.45-0.89). When stratified by gender and age, the individuals carrying at least one rs7869402T allele significantly decreased the NSCLC risk among males (OR?=?0.58, 95% CI?=?0.38-0.87) and among youngsters (OR?=?0.43, 95% CI?=?0.27-0.69). Smoking stratification analysis showed that the rs7869402T allele-containing genotype reduced the risk of NSCLC with OR (95% CI) of 0.50 (0.29-0.87) among smokers but not among nonsmokers (P > 0.05). When the individuals were classed by the pathological type, we found that the rs7869402T-containing genotype was associated with the risk of adenocarcinoma (OR?=?0.62, 95% CI?=?0.41-0.92) but not with that of squamous cell carcinoma (OR?=?0.71, 95% CI?=?0.44-1.13) and other types (OR?=?0.23, 95% CI?=?0.03-1.70). Compared with the TLR4 Ars1927914-Crs7869402-Trs11536891 haplotype, the Grs1927914-Trs7869402-Trs11536891 haplotype was associated with a decreased risk for developing NSCLC with OR (95% CI) of 0.57 (0.41-0.80). These results indicated that the TLR4 rs7869402 variation affects the genetic susceptibility to NSCLC.

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Impact of genetic variation in SORCS1 on memory retention.

Publications

Impact of genetic variation in SORCS1 on memory retention.

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