Variation at <it>APOE </it>and <it>STH </it>loci and Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>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 <it>APOE </it>gene and AD. Association between AD and the newly discovered saitohin (<it>STH</it>) gene, nested within the intron of the tau gene, has been reported. The present study aimed to elucidate the association between <it>APOE </it>and AD, and between <it>STH </it>and AD in our sample.</p> <p>Methods</p> <p>The functional polymorphisms, rs429358 and rs7412, in the <it>APOE </it>gene (which together define the <it>ε</it>2, <it>ε</it>3, and <it>ε</it>4 alleles), and the Q7R SNP in the <it>STH </it>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.</p> <p>Results</p> <p>Consistent with previously reported results, the frequencies of the <it>APOE ε</it>4 allele, <it>ε</it>4/<it>ε</it>4 genotype and <it>ε</it>3/<it>ε</it>4 genotype were significantly higher in AD cases than controls; the <it>ε</it>4/<it>ε</it>4 genotype frequency was significantly higher in early-onset AD (EOAD) than late-onset AD (LOAD); the frequencies of the <it>ε</it>2 allele, <it>ε</it>3 allele, <it>ε</it>3/<it>ε</it>3 genotype and <it>ε</it>2/<it>ε</it>3 genotype were significantly lower in AD cases than controls. Positive likelihood ratios (LRs⁺) of <it>APOE </it>alleles and genotypes increased in a linear trend with the number of <it>ε</it>4 alleles and decreased in a linear trend with the number of <it>ε</it>2 or <it>ε</it>3 alleles. There was no significant difference in the <it>STH </it>allele and genotype frequency distributions between AD cases and controls.</p> <p>Conclusion</p> <p>This study confirmed that the <it>ε</it>4 allele is a dose-response risk factor for AD and the <it>ε</it>4/<it>ε</it>4 genotype was associated with a significantly earlier age of onset. Moreover, we found that the <it>ε</it>2 allele was a dose-response protective factor for AD and the <it>ε</it>3 allele exerted a weaker dose-response protective effect for risk of AD compared with <it>ε</it>2. In a clinical setting, <it>APOE </it>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. <it>STH </it>variation was not significantly associated with AD in our sample.</p>

Abstract licence: CC BY-NC-ND

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