Variation at APOE and STH loci and Alzheimer's disease

被引：36

作者：

Zuo L. ^{[1
,2
]}

van Dyck C.H. ^{[3
]}

Luo X. ^{[1
,2
]}

Kranzler H.R. ^{[4
]}

Yang B.-Z. ^{[1
,2
]}

Gelernter J. ^{[1
,2
]}

机构：

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

[2] VA Connecticut Healthcare System, West Haven Campus, CT

[3] Alzheimer's Disease Research Unit, Department of Psychiatry, Yale University School of Medicine, New Haven, CT

[4] Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT

来源：

Behavioral and Brain Functions | / 2卷 / 1期

关键词：

Progressive Supranuclear Palsy; APOE Gene; APOE Allele; Genotype Frequency Distribution; KlenTaq Polymerase;

D O I：

10.1186/1744-9081-2-13

中图分类号：

学科分类号：

摘要：

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 allelles 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. © 2006 Zuo et al; licensee BioMed Central Ltd.

引用

共 45 条

[1]

Masters C., Simms G., Weinman N., Multhaup G., McDonald B., Beyreuther K., Amyloid plaque core protein in Alzheimer's disease and Down's syndrome, Proc Natl Acad Sci USA, 82, pp. 4245-4249, (1985)

[2]

Sennvik K., A study of β-secretase cleaved Alzheimer amyloid precursor protein, Novum, Huddinge, (2002)

[3]

Mahley R.W., Huang Y., Rall S.C., Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia). Questions, quandaries, and paradoxes, J Lipid Res, 40, pp. 1933-1949, (1999)

[4]

Puglielli L., Tanzi R.E., Kovacs D.M., Alzheimer's disease: The cholesterol connection, Nat Neurosci, 6, pp. 345-351, (2003)

[5]

Namba Y., Tomonaga M., Kawasaki H., Otomo E., Ikeda K., Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease, Brain Res, 541, pp. 163-166, (1991)

[6]

Munson G.W., Roher A.E., Kuo Y.M., Gilligan S.M., Reardon C.A., Getz G.S., LaDu M.J., SDS-Stable Complex Formation between Native Apolipoprotein E3 and β-Amyloid Peptides, Biochemistry, 39, pp. 16119-16124, (2000)

[7]

Kosik K., Joachim C., Selkoe D.J., Microtubule-associated protein tau (τ) is a major antigenic component of paired helical filaments in Alzheimer's disease, Proc Natl Acad Sci, 83, pp. 4044-4048, (1986)

[8]

Farrer M., Skipper L., Berg M., Bisceglio G., Hanson M., Hardy J., Adam A., Gwinn-Hardy K., Aasly J., The tau HI haplotype is associated and the risk of Alzheimer disease among African Americans, Whites, and Hispanics, J Am Med Assoc, 279, pp. 751-755, (1998)

[9]

Lilius L., Froelich Fabre S., Basun H., Forsell C., Axelman K., Mattila K., Andreadis A., Viitanen M., Winblad B., Fratiglioni L., Lannfelt L., Tau gene polymorphisms and apolipoprotein E epsilon4 may interact to increase risk for Alzheimer's disease, Neurosci Lett, 277, pp. 29-32, (1999)

[10]

Bullido M.J., Aldudo J., Frank A., Coria F., Avila J., Valdivieso F., A polymorphism in the tau gene associated with risk for Alzheimer's disease, Neurosci Lett, 278, pp. 49-52, (2000)

← 1 2 3 4 5 →