Polito Letizia, Prato Francesca, Rodilossi Serena, Ateri Eleonora, Galimberti Daniela, Scarpini Elio, Clerici Francesca, Mariani Claudio, Forloni Gianluigi, Albani Diego
Department of Neuroscience, Mario Negri Institute for Pharmacological Research, 20156 Milan, Italy.
Int J Alzheimers Dis. 2011;2011:312341. doi: 10.4061/2011/312341. Epub 2011 Jun 2.
Alzheimer's disease (AD) is a neurodegenerative disorder whose clinical onset is mainly characterized by memory loss. During AD progression, behavioral and psychological symptoms of dementia (BPSD) frequently occur. In this paper we evaluated the association between AD and the short/long (S/L) functional polymorphism of the promoter region of the 5-hydroxytryptamine (5-HT) transporter gene (SLC6A4). The S-allele shows a 2-fold reduced transcriptional rate, causing an imbalance in 5-HT intracellular availability that might in turn trigger behavioral and cognitive alterations. We also genotyped the SLC6A4 promoter functional variant rs25531 (A → G). By comparing the genotypic and allelic frequencies in an Italian population of 235 AD and 207 controls, we found an association between 5-HTTLPR and AD (odds ratio for the L-allele versus the S-allele: 0.74, associated P value = .03), while no difference was found for the rs25531. A meta-analysis of studies in Italy assessing 5-HTTLPR and AD risk gave an estimation of odds ratio for the L-allele versus the S-allele of 0.85 (associated P value = .08). Overall, our findings are not supportive of a large genetic effect of the explored polymorphisms on AD risk.
阿尔茨海默病（AD）是一种神经退行性疾病，其临床发病主要特征为记忆丧失。在AD进展过程中，痴呆的行为和心理症状（BPSD）经常出现。在本文中，我们评估了AD与5-羟色胺（5-HT）转运体基因（SLC6A4）启动子区域的短/长（S/L）功能多态性之间的关联。S等位基因的转录率降低了2倍，导致5-HT细胞内可用性失衡，进而可能引发行为和认知改变。我们还对SLC6A4启动子功能变体rs25531（A→G）进行了基因分型。通过比较235名AD患者和207名对照的意大利人群中的基因型和等位基因频率，我们发现5-HTTLPR与AD之间存在关联（L等位基因与S等位基因的优势比：0.74，相关P值=0.03），而rs25531未发现差异。对意大利评估5-HTTLPR与AD风险的研究进行的荟萃分析得出，L等位基因与S等位基因的优势比估计为0.85（相关P值=0.08）。总体而言，我们的研究结果不支持所探索的多态性对AD风险有较大的遗传影响。
