Variant "APOE:c.-491A>T"
Search results: 2 records
Variant information
Gene:
APOE 
Variant:
APOE:c.-491A>T 
dbSNP ID:
no data 
GWAS trait:
no data 
Modifier statisitcs
Record:
2 
Disorder:
1 
Reference:
2 
Effect type:
Expressivity(2)  
Modifier effect:
Altered cognitive performances(1) ,Altered intraocular pressure(1)  
Details：
  • Target disease:
    Alzheimer's Disease (DOID_10652)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered cognitive performances 
    Evidence:
    Assessment of genotype–phenotype associations 
    Effect:
    Patients carrying the -491 AA genotype had poorer cognitive performances than the -491 AT ones,
    Reference:
    PMID20152880
    Title:
    The APOE-491 A/T promoter polymorphism effect on cognitive profile of Alzheimer's patients.
    Species studied:
    Human
    Abstract:
    Alzheimer's Disease (AD) is a neurodegenerative disorder with a complex aetiology displayed by multiple pathogenic factors. The APOE varepsilon4 allele represents the only established genetic risk factor for sporadic AD; in addition, previous findings on three single nucleotide polymorphisms (SNPs) located on the APOE promoter region, have led to a growing interest in their potential role in AD pathogenesis. The -491 A/T promoter polymorphism has been the one most frequently shown to be associated with AD, as it influences the APOE coding region transcription. The aim of this study was to evaluate the possible effect of the -491 A/T polymorphism on the cognitive profile of sporadic AD patients with a disease severity ranging from mild to moderate. Our results showed that patients carrying the -491 AA genotype had poorer cognitive performances than the -491 AT ones, statistically significant in demanding tests of visual attention, especially for the late-onset AD (LOAD). No further differences on cognitive profile were observed when stratifying AA and AT patients according to their APOE genotype. These results suggest a possible functional effect of the -491 A/T promoter on the neuropsychological performances of AD. This role seems to be independent of APOE genotype. In fact the effect of -491 A/T occurs predominantly on attention while the APOE varepsilon4 allele mainly affects memory performances. According to the biological effect exerted on APOE transcription, the -491 A/T polymorphism could be considered a disease modifier more than a risk factor for sporadic AD.
  • Target disease:
    Alzheimer's Disease (DOID_10652)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered intraocular pressure 
    Evidence:
    Gene activity study 
    Effect:
    APOE(-491T) is associated with increased intraocular pressure (IOP) and with limited effectiveness of IOP-lowering treatments in patients with POAG.
    Reference:
    PMID11992263
    Title:
    Apolipoprotein E-promoter single-nucleotide polymorphisms affect the phenotype of primary open-angle glaucoma and demonstrate interaction with the myocilin gene.
    Species studied:
    Human
    Abstract:
    Primary open-angle glaucoma (POAG) is an optic neuropathy that has a high worldwide prevalence and that shows strong evidence of complex inheritance. The myocilin (MYOC) gene is the only one that has thus far been shown to have mutations in patients with POAG. Apolipoprotein E (APOE) plays an essential role in lipid metabolism, and the APOE gene has been involved in neuronal degeneration that occurs in Alzheimer disease (AD). Here, we report that two APOE-promoter single-nucleotide polymorphisms (SNPs) previously associated with AD also modify the POAG phenotype. APOE(-219G) is associated with increased optic nerve damage, as reflected by increased cup:disk ratio and visual field alteration. In addition, APOE(-491T), interacting at a highly significant level with an SNP in the MYOC promoter, MYOC(-1000G), is associated with increased intraocular pressure (IOP) and with limited effectiveness of IOP-lowering treatments in patients with POAG. Together, these findings establish APOE as a potent modifier for POAG, which could explain the linkage to chromosome 19q previously observed by use of a genome scan for this condition and an increased frequency of glaucoma in patients with AD. The findings also shed new light on potential mechanisms of optic nerve damage and of IOP regulation in POAG.