Porrello E, Monti M C, Sinforiani E, Cairati M, Guaita A, Montomoli C, Govoni S, Racchi M
Department of Experimental and Applied Pharmacology, Section of Medical Statistics and Epidemiology, University of Pavia, Italy.
Eur J Neurol. 2006 Jun;13(6):639-44. doi: 10.1111/j.1468-1331.2006.01333.x.
Alzheimer's disease (AD) is a progressive neurodegenerative disease that affects both sexes, with a higher prevalence in women. Declining estrogen levels after menopause may render estrogen target neurons in the brain more susceptible to age or disease-related processes such as AD. To investigate the role of two single nucleotide polymorphisms in the first intron of the ER-alpha gene, denominated PvuII and XbaI, and their interaction with the known AD susceptibility gene APOE, we examined 131 patients with sporadic AD and 109 healthy control subjects. In multinomial logistic regression analysis, a significantly increased risk of sporadic AD because of interaction between the ER-alpha p allele and APOE epsilon4 allele was observed in women, taking subjects who had neither the p allele nor epsilon4 as reference [odds ratio (OR) 7.24; 95% CI, 2.22-23.60]. For women carrying the ER-alpha x allele together with APOE epsilon4, the risk of sporadic AD was similarly elevated (OR 8.33; 95% CI, 1.73-40.06). The data suggest that the p and x alleles of polymorphic ER-alpha gene interact synergistically with the APOE epsilon4 allele to increase the risk of AD in women but not in men in this Italian cohort.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，影响两性，女性患病率更高。绝经后雌激素水平下降可能使大脑中的雌激素靶神经元更容易受到与年龄或疾病相关的过程影响，如AD。为了研究雌激素受体α（ER-α）基因第一个内含子中两个单核苷酸多态性（分别命名为PvuII和XbaI）的作用，以及它们与已知的AD易感基因载脂蛋白E（APOE）的相互作用，我们检查了131例散发性AD患者和109名健康对照者。在多项逻辑回归分析中，以既没有p等位基因也没有ε4等位基因的受试者为参照，观察到女性中由于ER-α p等位基因与APOE ε4等位基因相互作用导致散发性AD风险显著增加[比值比（OR）7.24；95%置信区间（CI），2.22 - 23.60]。对于同时携带ER-α x等位基因和APOE ε4的女性，散发性AD风险同样升高（OR 8.33；95% CI，1.73 - 40.06）。数据表明，在这个意大利队列中，多态性ER-α基因的p和x等位基因与APOE ε4等位基因协同作用，增加女性而非男性患AD的风险。
