Lack of Association between Interleukin-1 alpha rs1800587 Polymorphism and Alzheimer's Disease in Two Independent European Samples

Article type: Research Article

Authors: Serretti, Alessandro^{a; *} | Olgiati, Paolo^a | Politis, Antonis^b | Malitas, Petros^c | Albani, Diego^d | Dusi, Sabrina^d | Polito, Letizia^d | De Mauro, Stefania^d | Zisaki, Aikaterini^e | Piperi, Christina^e | Liappas, Ioannis^f | Stamouli, Evangelia^b | Mailis, Antonis^b | Atti, Anna Rita^a | Morri, Monica^a | Ujkaj, Manjola^a | Batelli, Sara^d | Forloni, Gianluigi^d | Soldatos, Costantine R.^f | Papadimitriou, George N.^f | De Ronchi, Diana^a | Kalofoutis, Anastasios^{e; g}

Affiliations: [a] Institute of Psychiatry, University of Bologna, Bologna, Italy | [b] Division of Geriatric Psychiatry Department of Psychiatry, Eginition Hospital, University of Athens Medical School, Athens, Greece | [c] Vice President of the European Centre for the Quality of Life – E.C.Qua.L., Athens, Greece | [d] Neuroscience Department, Istituto di ricerche Farmacologiche “Mario Negri”, Milan, Italy | [e] Laboratory of Biological Chemistry, University of Athens Medical School, Athens, Greece | [f] Department of Psychiatry, Eginition Hospital, University of Athens Medical School, Athens, Greece | [g] President of the European Centre for the Quality of Life – E.C.Qua.L., Athens, Greece

Correspondence: [*] Corresponding author: Alessandro Serretti, Institute of Psychiatry, University of Bologna, Viale Carlo Pepoli 5, 40123 Bologna, Italy. Tel.: +39 051 6584233; Fax: +39 051 521030; E-mail: [email protected].

Abstract: Interleukin-1 (IL1) can contribute to pathophysiology of Alzheimer's disease (AD) by promoting deposition of amyloid-β in the brain. The gene encoding IL1 alpha (IL1A) has a common polymorphism in its 5' regulatory region (rs1800587) with possible functional effects. IL1A T/T genotype has been associated with AD but the overall effect is modest and negative studies have been published. The aim of this study was to investigate the association of the IL1A rs1800587 polymorphism with AD in two independent case-control groups from Greece (Athens) and Italy (Faenza and Granarolo). Preliminary results from the ongoing sample (110 patients with sporadic AD and 130 nonpsychiatric controls) showed no association between IL1A variants and AD, however C/T heterozygotes had more severe depression in AD (Cornell Scale for Depression in Dementia) compared to other genotypes (F=4.56, d.f=1, p=0.037) after controlling for age, illness duration and cognitive impairment (MMSE). Despite the small sample size and the possibility of a false negative finding, our preliminary data support the hypothesis the IL1A rs1800587 variants are not associated with AD. The effect of the IL1A on depressive symptomatology warrants further investigations, however the lack of a gene-dose relationship would suggest a false positive.

Keywords: Alzheimer's disease, IL-1A gene, inflammatory cytokines, psychosis

DOI: 10.3233/JAD-2009-0946

Journal: Journal of Alzheimer's Disease, vol. 16, no. 1, pp. 181-187, 2009