Dataset Information

SORL1 gene, plasma biomarkers, and the risk of Alzheimer's disease for the Han Chinese population in Taiwan.

ABSTRACT: The sortilin-related receptor 1 (SORL1) gene, regulating the trafficking and recycling of amyloid precursor protein, has been related to Alzheimer's disease (AD) and mild cognitive impairment (MCI). The aim of the present study was to investigate the relationship between SORL1 polymorphisms, plasma concentrations of amyloid-beta (A?) isoforms, and AD and MCI susceptibility for a Han Chinese population in Taiwan.Eight single-nucleotide polymorphisms (SNPs) in SORL1 and the apolipoprotein E gene (APOE) ?4 alleles were genotyped in 798 patients with AD, 157 patients with MCI, and 401 control subjects. Plasma concentrations of A?42, A?40, and neuropsychiatric tests for six different cognitive domains were examined.Among the eight tested SNPs, SORL1 rs1784933 was most significantly associated with AD and MCI in our population. The G allele of rs1784933 exerted a protective effect and was associated with a reduced risk of AD (odds ratio [OR]?=?0.75, p?=?0.004) and MCI (OR?=?0.69, p?=?0.013). The significance remained after we adjusted for age, sex, and APOE ?4 alleles. For the overall participants, the plasma concentrations of A?42 were nominally significant for subjects carrying the rs1784933 G allele having a lower level than those without the G allele (p?=?0.046). There was a similar trend for the G allele carriers to have a lower plasma A?40 level than noncarriers, but this was not significant. The nonsynonymous SNP rs2298813 was also related to a lower disease risk when AD and MCI were combined as a group (OR?=?0.76, p?=?0.035). However, there was no association between SORL1 genotypes and any of the six cognitive tests.Findings from our study provide support for the effect of SORL1 gene on the disease risks and pathognomonic surrogates of AD/MCI. The interaction between SORL1 polymorphisms and A? formation requires further study.

SUBMITTER: Chou CT

PROVIDER: S-EPMC5200969 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SORL1 gene, plasma biomarkers, and the risk of Alzheimer's disease for the Han Chinese population in Taiwan.

Chou Cheng-Ta CT Liao Yi-Chu YC Lee Wei-Ju WJ Wang Shuu-Jiun SJ Fuh Jong-Ling JL

Alzheimer's research & therapy 20161230 1

<h4>Background</h4>The sortilin-related receptor 1 (SORL1) gene, regulating the trafficking and recycling of amyloid precursor protein, has been related to Alzheimer's disease (AD) and mild cognitive impairment (MCI). The aim of the present study was to investigate the relationship between SORL1 polymorphisms, plasma concentrations of amyloid-beta (Aβ) isoforms, and AD and MCI susceptibility for a Han Chinese population in Taiwan.<h4>Methods</h4>Eight single-nucleotide polymorphisms (SNPs) in SO ...[more]

PMID: 28034305

Similar Datasets

Project description:BackgroundSchizophrenia is a highly heritable disease with a polygenic mode of inheritance. Many studies have contributed to our understanding of the genetic underpinnings of schizophrenia, but little is known about how interactions among genes affect the risk of schizophrenia. This study aimed to assess the associations and interactions among genes that confer vulnerability to schizophrenia and to examine the moderating effect of neuropsychological impairment.MethodsWe analyzed 99 SNPs from 10 candidate genes in 1,512 subject samples. The permutation-based single-locus, multi-locus association tests, and a gene-based multifactorial dimension reduction procedure were used to examine genetic associations and interactions to schizophrenia.ResultsWe found that no single SNP was significantly associated with schizophrenia. However, a risk haplotype, namely A-T-C of the SNP triplet rsDAO7-rsDAO8-rsDAO13 of the DAO gene, was strongly associated with schizophrenia. Interaction analyses identified multiple between-gene and within-gene interactions. Between-gene interactions including DAO*DISC1 , DAO*NRG1 and DAO*RASD2 and a within-gene interaction for CACNG2 were found among schizophrenia subjects with severe sustained attention deficits, suggesting a modifying effect of impaired neuropsychological functioning. Other interactions such as the within-gene interaction of DAO and the between-gene interaction of DAO and PTK2B were consistently identified regardless of stratification by neuropsychological dysfunction. Importantly, except for the within-gene interaction of CACNG2, all of the identified risk haplotypes and interactions involved SNPs from DAO.ConclusionsThese results suggest that DAO, which is involved in the N-methyl-d-aspartate receptor regulation, signaling and glutamate metabolism, is the master gene of the genetic associations and interactions underlying schizophrenia. Besides, the interaction between DAO and RASD2 has provided an insight in integrating the glutamate and dopamine hypotheses of schizophrenia.

Dataset Information

SORL1 gene, plasma biomarkers, and the risk of Alzheimer's disease for the Han Chinese population in Taiwan.

Publications

SORL1 gene, plasma biomarkers, and the risk of Alzheimer's disease for the Han Chinese population in Taiwan.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets