Cellini Elena, Tedde Andrea, Bagnoli Silvia, Nacmias Benedetta, Piacentini Silvia, Bessi Valentina, Bracco Laura, Sorbi Sandro
Department of Neurological and Psychiatric Sciences, University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy.
Neurosci Lett. 2006 Nov 20;408(3):199-202. doi: 10.1016/j.neulet.2006.08.074. Epub 2006 Sep 25.
Genetic variants in the paraoxonase (PON) gene cluster, particularly a single C/T promoter polymorphism (rs 705381) in the PON-1 gene, have recently been associated with Alzheimer's disease (AD). The T allele, in particular, presents an increased risk for the development of AD. Here, we investigate the potential role of this polymorphism in an Italian case-control population consisting of 306 sporadic AD patients and 275 controls, and also evaluate a possible interaction with the ApoE genotype. No association between the PON-1 polymorphism and AD was observed. The T allele frequency was slightly over-represented in AD patients compared to the controls, but this was far from being statistically significant. Our sample was evaluated to have 97.3% power to detect an OR of 2.0 (64.3% power with OR=1.5) at an alpha level of 0.05. No evidence of an interaction between the T risk-allele and the ApoE epsilon4 allele status and no effect of the PON-1 polymorphism on age at onset was detected. Our results do not support other studies indicating that the PON-1 promoter polymorphism plays a major role in AD, suggesting that other large studies are necessary to further elucidate the effect of PON on the development of the disease in the general population.
对氧磷酶（PON）基因簇中的遗传变异，尤其是对氧磷酶-1（PON-1）基因中的单个C/T启动子多态性（rs 705381），最近已被证实与阿尔茨海默病（AD）相关。特别是T等位基因，会增加患AD的风险。在此，我们研究了这种多态性在一个意大利病例对照人群中的潜在作用，该人群由306例散发性AD患者和275例对照组成，同时还评估了与载脂蛋白E（ApoE）基因型的可能相互作用。未观察到PON-1多态性与AD之间存在关联。与对照组相比，AD患者中T等位基因频率略高，但远未达到统计学显著性。我们的样本在α水平为0.05时，检测比值比（OR）为2.0的效能为97.3%（OR = 1.5时效能为64.3%）。未检测到T风险等位基因与ApoE ε4等位基因状态之间存在相互作用的证据，也未检测到PON-1多态性对发病年龄有影响。我们的结果不支持其他研究表明PON-1启动子多态性在AD中起主要作用的观点，这表明需要其他大规模研究来进一步阐明PON对一般人群中该疾病发展的影响。
