Association between Sirtuin 2 gene rs10410544 polymorphism and depression in Alzheimer’s disease in two independent European samples
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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.
KeywordsAlzheimer’s disease Depression SIRT2 gene Inflammatory cytokines
The research at Istituto di Ricerche Famacologiche “Mario Negri” was supported by Fondazione Italo Monzino, Milan, Italy.
Conflict of interest
No conflict of interest is present for the authors.
- American Psychiatric Association., American Psychiatric Association. Task Force on DSM-IV (2000) Diagnostic and statistical manual of mental disorders: DSM-IV-TR. 4th edn. American Psychiatric Association, WashingtonGoogle Scholar
- Bufalino C, Hepgul N, Aguglia E, Pariante CM (2012) The role of immune genes in the association between depression and inflammation: a review of recent clinical studies. Brain Behav Immun doi: 10.1016/j.bbi.2012.04.009
- De Ronchi D, Berardi D, Menchetti M, Ferrari G, Serretti A, Dalmonte E, Fratiglioni L (2005) Occurrence of cognitive impairment and dementia after the age of 60: a population-based study from Northern Italy. Dement Geriatr Cogn Disord 19(2–3):97–105. doi: 10.1159/000082660 PubMedCrossRefGoogle Scholar
- Drago V, Babiloni C, Bartres-Faz D, Caroli A, Bosch B, Hensch T, Didic M, Klafki HW, Pievani M, Jovicich J, Venturi L, Spitzer P, Vecchio F, Schoenknecht P, Wiltfang J, Redolfi A, Forloni G, Blin O, Irving E, Davis C, Hardemark HG, Frisoni GB (2011) Disease tracking markers for Alzheimer’s disease at the prodromal (MCI) stage. J Alzheimers Dis 26(Suppl 3):159–199. doi: 10.3233/JAD-2011-0043 PubMedGoogle Scholar
- Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M (2005) Global prevalence of dementia: a Delphi consensus study. Lancet 366(9503):2112–2117. doi: 10.1016/S0140-6736(05)67889-0 PubMedCrossRefGoogle Scholar
- Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L et al (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 349(6311):704–706. doi: 10.1038/349704a0 PubMedCrossRefGoogle Scholar
- Kim HS, Vassilopoulos A, Wang RH, Lahusen T, Xiao Z, Xu X, Li C, Veenstra TD, Li B, Yu H, Ji J, Wang XW, Park SH, Cha YI, Gius D, Deng CX (2011) SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. Cancer Cell 20(4):487–499. doi: 10.1016/j.ccr.2011.09.004 PubMedCrossRefGoogle Scholar
- Olgiati P, Politis A, Malitas P, Albani D, Dusi S, Polito L, De Mauro S, Zisaki A, Piperi C, Stamouli E, Mailis A, Batelli S, Forloni G, De Ronchi D, Kalofoutis A, Liappas I, Serretti A (2010) APOE epsilon-4 allele and cytokine production in Alzheimer’s disease. Int J Geriatr Psychiatry 25(4):338–344. doi: 10.1002/gps.2344 PubMedCrossRefGoogle Scholar
- Olgiati P, Politis A, Albani D, Rodilossi S, Polito L, Ateri E, Zisaki A, Piperi C, Liappas I, Stamouli E, Mailis A, Atti AR, Ferrari B, Morini V, Moretti F, Biella G, Forloni G, Papadimitriou GN, Ronchi DD, Kalofoutis A, Serretti A (2012) Association of SORL1 alleles with late-onset Alzheimer’s disease. findings from the GIGAS_LOAD study and mega-analysis. Curr Alzheimer Res 9(4):491–499PubMedCrossRefGoogle Scholar
- Politis A, Olgiati P, Malitas P, Albani D, Signorini A, Polito L, De Mauro S, Zisaki A, Piperi C, Stamouli E, Mailis A, Batelli S, Forloni G, De Ronchi D, Kalofoutis A, Liappas I, Serretti A (2010) Vitamin B12 levels in Alzheimer’s disease: association with clinical features and cytokine production. J Alzheimers Dis 19(2):481–488. doi: 10.3233/JAD-2010-1252 PubMedGoogle Scholar
- Polito L, Kehoe PG, Davin A, Benussi L, Ghidoni R, Binetti G, Quadri P, Lucca U, Tettamanti M, Clerici F, Bagnoli S, Galimberti D, Nacmias B, Sorbi S, Guaita A, Scarpini E, Mariani C, Forloni G, Albani D (2012) The SIRT2 polymorphism rs10410544 and risk of Alzheimer’s disease in two Caucasian case-control cohorts. Alzheimers Dement doi: 10.1016/j.jalz.2012.02.003
- Serretti A, Olgiati P, Politis A, Malitas P, Albani D, Dusi S, Polito L, De Mauro S, Zisaki A, Piperi C, Liappas I, Stamouli E, Mailis A, Atti AR, Morri M, Ujkaj M, Batelli S, Forloni G, Soldatos CR, Papadimitriou GN, De Ronchi D, Kalofoutis A (2009) Lack of association between interleukin-1 alpha rs1800587 polymorphism and Alzheimer’s disease in two independent European samples. J Alzheimers Dis 16(1):181–187. doi: 10.3233/JAD-2009-0946 PubMedGoogle Scholar
- Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, Tsuda T, Mar L, Foncin JF, Bruni AC, Montesi MP, Sorbi S, Rainero I, Pinessi L, Nee L, Chumakov I, Pollen D, Brookes A, Sanseau P, Polinsky RJ, Wasco W, Da Silva HA, Haines JL, Perkicak-Vance MA, Tanzi RE, Roses AD, Fraser PE, Rommens JM, St George-Hyslop PH (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature 375(6534):754–760. doi: 10.1038/375754a0 PubMedCrossRefGoogle Scholar