Abstract
BackgroundThe apolipoprotein E (APOE) and tau proteins play important roles in the pathological development of Alzheimer's disease (AD). Many studies have shown an association between the APOE gene and AD. Association between AD and the newly discovered saitohin (STH) gene, nested within the intron of the tau gene, has been reported. The present study aimed to elucidate the association between APOE and AD, and between STH and AD in our sample.MethodsThe functional polymorphisms, rs429358 and rs7412, in the APOE gene (which together define the ε2, ε3, and ε4 alleles), and the Q7R SNP in the STH gene, were genotyped in 369 patients with AD and 289 healthy European-Americans. The associations between these two genes and AD were analyzed in a case-control design.ResultsConsistent with previously reported results, the frequencies of the APOE ε4 allele, ε4/ε4 genotype and ε3/ε4 genotype were significantly higher in AD cases than controls; the ε4/ε4 genotype frequency was significantly higher in early-onset AD (EOAD) than late-onset AD (LOAD); the frequencies of the ε2 allele, ε3 allele, ε3/ε3 genotype and ε2/ε3 genotype were significantly lower in AD cases than controls. Positive likelihood ratios (LRs+) of APOE alleles and genotypes increased in a linear trend with the number of ε4 alleles and decreased in a linear trend with the number of ε2 or ε3 alleles. There was no significant difference in the STH allele and genotype frequency distributions between AD cases and controls.ConclusionThis study confirmed that the ε4 allele is a dose-response risk factor for AD and the ε4/ε4 genotype was associated with a significantly earlier age of onset. Moreover, we found that the ε2 allele was a dose-response protective factor for AD and the ε3 allele exerted a weaker dose-response protective effect for risk of AD compared with ε2. In a clinical setting, APOE genotyping could offer additional biological evidence of whether a subject may develop AD, but it is not robust enough to serve as an independent screening or predictive test in the diagnosis of AD. STH variation was not significantly associated with AD in our sample.
Highlights
The apolipoprotein E (APOE) and tau proteins play important roles in the pathological development of Alzheimer's disease (AD)
Associations of APOE alleles and genotypes with Alzheimer's disease The comparisons of allele and genotype frequency distributions between AD cases and controls are shown in Tables 1 and 2
The genotype frequency distributions in both AD cases and controls were in Hardy-Weinberg equilibrium (HWE)
Summary
The apolipoprotein E (APOE) and tau proteins play important roles in the pathological development of Alzheimer's disease (AD). Many studies have shown an association between the APOE gene and AD. Alzheimer's disease (AD) is the most common cause of dementia. It is a primary neurodegenerative cerebral disease in the elderly, characterized by two major histopathologic changes in the brain, i.e., extracellular amyloid plaques and intracellular neurofibrillary tangles [1,2]. Apolipoprotein E (APOE) is one of the major cholesterol transport proteins. It exists in three major isoforms, APOE2, APOE3 and APOE4. Studies have shown that APOE interacts with Aβ to form a stable complex, altering the deposition of Aβ and affecting Aβ-induced neurotoxicity [6]
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