MCP-1 A-2518G Polymorphism: Effect on Susceptibility for Frontotemporal Lobar Degeneration and on Cerebrospinal Fluid MCP-1 Levels

Article type: Research Article

Authors: Galimberti, Daniela^{a; *} | Venturelli, Eliana^a | Villa, Chiara^a | Fenoglio, Chiara^a | Clerici, Francesca^b | Marcone, Alessandra^c | Benussi, Luisa^d | Cortini, Francesca^a | Scalabrini, Diego^a | Perini, Luca^a | Restelli, Ilaria^a | Binetti, Giuliano^d | Cappa, Stefano^{c; e} | Mariani, Claudio^b | Bresolin, Nereo^a | Scarpini, Elio^a

Affiliations: [a] Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy | [b] Centre for Research and Treatment on Cognitive Dysfunctions, Chair of Neurology, University of Milan, “Luigi Sacco” Hospital, Milan, Italy | [c] Division of Neurology, San Raffaele Turro Hospital, San Raffaele Scientific Institute, Milan, Italy | [d] NeuroBioGen-Lab-Memory Clinic, IRCCS Centro S.Giovanni di Dio-Fatebenefratelli, Brescia, Italy | [e] Vita-Salute San Raffaele University, Milan, Italy

Correspondence: [*] Corresponding author: Daniela Galimberti, Department of Neurological Sciences, "Dino Ferrari" Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy. Tel.: +39 2 55033858; Fax: +39 2 50320430; E-mail: [email protected].

Abstract: The distribution of the MCP-1 A-2518G single nucleotide polymorphisms (SNP) was analyzed in a population of 212 patients with frontotemporal lobar degeneration (FTLD) compared with 203 age-matched controls. A significantly decreased allelic frequency of the G allele in patients compared with controls was observed (21.1 versus 29.3%, P = 0.011, OR: 0.59, CI: 0.40–0.87). Stratifying according to gender, the association was maintained in male patients versus male controls (17.8 versus 29.4%, P = 0.016, OR = 0.46, 95% CI: 0.25–0.84), but not in female patients compared with female controls (23.5 versus 29.2%, P > 0.05). The frequency of apolipoprotein E ε4 carriers was increased in patients (26.4 versus 13.8%, P = 0.0015, OR: 2.24, 95% CI: 1.37–3.67). Apolipoprotein E status did not influence the distribution of the A-2518G SNP. Monocyte chemotactic protein (MCP)-1 levels were determined in cerebrospinal fluid (CSF) collected from 23 patients and 17 controls. MCP-1 CSF levels were increased in patients compared with controls (449.01 ± 27.57 versus 364.19 ± 23.75 pg/ml, P = 0.011). Stratifying patients according to the presence of the polymorphic allele, significantly increased CSF MCP-1 levels were observed in carriers of the G allele compared with non-carriers (502.21 ± 44.57 versus 395.87 ± 21.92 pg/ml, P = 0.045). The MCP-1 A-2518G SNP acts as protective factor for sporadic FTLD, possibly by influencing MCP-1 production.

Keywords: Cerebrospinal fluid, monocyte chemotactic protein-1, risk factor, single nucleotide polymorphism, sporadic frontotemporal lobar degeneration

DOI: 10.3233/JAD-2009-1019

Journal: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 125-133, 2009