Association between Sirtuin 2 gene rs10410544 polymorphism and depression in Alzheimer's disease in two independent European samples.

Abstract

Among the several genes associated with late-onset Alzheimer's disease (LOAD), recently, Sirtuin genes have roused a growing interest because of their involvement in metabolic homeostasis and in brain aging. Particularly SIRT2 gene has been associated with Alzheimer's disease (AD) as well as with mood disorders. The aim of this study is to investigate the possible associations between Sirtuin 2 gene (SIRT2) rs10410544 polymorphism and AD as well as depression in AD. In addition, we performed some exploratory analyses to investigate possible associations between the rs10410544 genotype and clinical features. We investigated these associations in two independent samples: the first one was composed of 275 Greek inhabitants and 117 patients; the second sample counted 181 Italian people and 43 patients. All patients were affected by LOAD. We failed to find any association between rs10410544 genotype and AD in the two samples. On the other hand, we found an association between the single nucleotide polymorphism (SNP) and depressive symptomatology (in the total sample p = 0.002), which was modulated by the tumor necrosis factor (TNF) values. Particularly, TT genotype seems to be protective versus depression. Finally, in the exploratory analyses, we found that the TT genotype was associated with earlier AD onset and a longer duration of the illness. In conclusion, we confirmed the association between SIRT2 gene and mood disturbances, although in AD patients. Further, we provided evidence that the TT genotype may be protective versus depressive symptoms, allowing an easier and thus earlier diagnosis of AD. This awareness may lead to a more detailed approach to these patients concerning diagnosis and therapy.

• Authors: Stefano Porcelli, Raffaele Salfi, Antonis Politis, Anna Rita Atti, Diego Albani, Armando Chierchia, Letizia Polito, Aikaterini Zisaki, Christina Piperi, Ioannis Liappas, Siegfried Alberti, Martina Balestri, Agnese Marsano, Evangelia Stamouli, Antonis Mailis, Gloria Biella, Gianluigi Forloni, Virginia Bernabei, Barbara Ferrari, Loredana Lia, George N Papadimitriou, Diana De Ronchi, Alessandro Serretti
• Journal: Journal of neural transmission (Vienna, Austria : 1996) (J Neural Transm (Vienna)) Vol. 120 Issue 12 Pg. 1709-15 (Dec 2013) ISSN: 1435-1463 [Electronic] Austria
• PMID: 23712749 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• SIRT2 protein, human
• Sirtuin 2

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (complications, genetics)
• Analysis of Variance
• Depression (etiology, genetics)
• Female
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genotype
• Greece
• Humans
• Italy
• Male
• Polymorphism, Single Nucleotide (genetics)
• Psychiatric Status Rating Scales
• Sirtuin 2 (genetics)