Clinical Neurosciences Department, San Raffaele Turro Hospital, Vita-Salute San Raffaele University, via Stamira D'Ancona 20, Milan, Italy.
Neurol Sci. 2010 Dec;31(6):741-9. doi: 10.1007/s10072-010-0400-8. Epub 2010 Sep 18.
Serotonergic transmission impairment and abnormal phosphorylation of tau protein have been implicated in the physiopathology of Alzheimer's disease (AD) and frontotemporal lobar dementia (FTLD). Associations between a functional polymorphism (5-HTTLPR), in the promoter region of the serotonin transporter gene, and susceptibility to sporadic AD and FTLD have been reported. A polymorphism (Q7R) in saitohin gene inside the microtubule-associated protein tau gene has also been related to dementia. To determine the possible role of the two polymorphisms in susceptibility to AD and FTLD, we performed a case-control study collecting 218 Italian sporadic dementia patients and 54 controls. We found a significant excess of 5-HTTLPR short alleles and an interaction between 5-HTTLPR and Q7R polymorphisms in demented subjects. Our study confirms the role of 5-HTTLPR as a potential susceptibility factor for sporadic dementia in the Italian population, and suggests a possible interaction between 5-HTTLPR and Q7R polymorphisms in neurodegenerative diseases.
5-羟色胺能传递损伤和 tau 蛋白异常磷酸化与阿尔茨海默病（AD）和额颞叶痴呆（FTLD）的病理生理学有关。在 5-羟色胺转运体基因启动子区域的功能性多态性（5-HTTLPR）与散发性 AD 和 FTLD 的易感性之间存在关联。微管相关蛋白 tau 基因内的 saitohin 基因（Q7R）的多态性也与痴呆有关。为了确定这两种多态性在 AD 和 FTLD 易感性中的可能作用，我们进行了一项病例对照研究，收集了 218 名意大利散发性痴呆患者和 54 名对照。我们发现，在痴呆患者中，5-HTTLPR 短等位基因明显过多，并且 5-HTTLPR 和 Q7R 多态性之间存在相互作用。我们的研究证实了 5-HTTLPR 作为意大利人群散发性痴呆的潜在易感因素的作用，并提示 5-HTTLPR 和 Q7R 多态性在神经退行性疾病中可能存在相互作用。
