Research

Variation at APOE and STH loci and Alzheimer's disease

Lingjun Zuo^1,2 , Christopher H van Dyck³ , Xingguang Luo^1,2 , Henry R Kranzler⁴ , Bao-zhu Yang^1,2 and Joel Gelernter^1,2

¹  Division of Human Genetics, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

²  VA Connecticut Healthcare System, West Haven Campus, CT, USA

³  Alzheimer's Disease Research Unit and Cognitive Disorders Clinic, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

⁴  Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA

author email corresponding author email

Behavioral and Brain Functions 2006, 2:13doi:10.1186/1744-9081-2-13

Published:	7 April 2006

Abstract

Background

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. 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.

Methods

The 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.

Results

Consistent 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.

Conclusion

This 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.