Variation at APOE and STH loci and Alzheimer's disease.
Variation at APOE and STH loci and Alzheimer's disease.
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DOI：
10.1186/1744-9081-2-13
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发表时间：
2006-04-07
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影响因子：
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通讯作者：
Gelernter, Joel
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文献类型：
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作者：
Zuo, Lingjun;van Dyck, Christopher H;Gelernter, Joel
背景：载脂蛋白E（apolipoprotein E，APOE）和tau蛋白在阿尔茨海默病（Alzheimer 'sdisease，AD）的病理过程中起重要作用。许多研究表明，APOE基因与AD之间存在关联。AD和新发现的saitohin（STH）基因之间的关联，嵌套在tau基因的内含子中，已经有报道。本研究旨在阐明APOE和AD之间的关联，STH和AD之间在我们的sample.METHODS：APOE基因的功能多态性，rs 429358和rs7412（共同定义ε 2，ε 3和ε 4等位基因），和Q7 R的SNP在STH基因，在369例AD患者和289名健康的欧洲裔美国人进行基因分型。结果：与以往报道的结果一致，AD患者中apoE ε 4等位基因、ε 4/ε 4基因型和ε 3/ε 4基因型的频率均显著高于对照组，早发性AD（EOAD）中ε 4/ε 4基因型的频率显著高于晚发性AD（LOAD）; AD组ε 2等位基因、ε 3等位基因、ε 3/ε 3基因型和ε 2/ε 3基因型频率均显著低于对照组。APOE等位基因和基因型的阳性似然比（LR+）随ε 4等位基因数的增加呈线性趋势，随ε 2或ε 3等位基因数的增加呈线性趋势。STH等位基因和基因型频率分布在AD病例和对照组之间无显著差异。结论：本研究证实ε 4等位基因是AD的剂量反应危险因素，ε 4/ε 4基因型与较早的发病年龄相关。此外，我们发现ε 2等位基因是AD的剂量-反应保护因子，ε 3等位基因对AD风险的剂量-反应保护作用较弱。在临床环境中，APOE基因分型可以提供受试者是否可能发展为AD的额外生物学证据，但它不足以作为诊断AD的独立筛查或预测测试。在我们的样本中，STH变异与AD无显著相关性。
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 epsilon2, epsilon3, and epsilon4 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 epsilon4 allele, epsilon4/epsilon4 genotype and epsilon3/epsilon4 genotype were significantly higher in AD cases than controls; the epsilon4/epsilon4 genotype frequency was significantly higher in early-onset AD (EOAD) than late-onset AD (LOAD); the frequencies of the epsilon2 allele, epsilon3 allele, epsilon3/epsilon3 genotype and epsilon2/epsilon3 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 epsilon4 alleles and decreased in a linear trend with the number of epsilon2 or epsilon3 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 epsilon4 allele is a dose-response risk factor for AD and the epsilon4/epsilon4 genotype was associated with a significantly earlier age of onset. Moreover, we found that the epsilon2 allele was a dose-response protective factor for AD and the epsilon3 allele exerted a weaker dose-response protective effect for risk of AD compared with epsilon2. 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.