MCP-1 A-2518G polymorphism: effect on susceptibility for frontotemporal lobar degeneration and on cerebrospinal fluid MCP-1 levels.
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 epsilon4 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.
Galimberti
Daniela
D
Department of Neurological Sciences, "Dino Ferrari" Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy. daniela.galimberti@unimi.it
Venturelli
Eliana
E
Villa
Chiara
C
Fenoglio
Chiara
C
Clerici
Francesca
F
Marcone
Alessandra
A
Benussi
Luisa
L
Cortini
Francesca
F
Scalabrini
Diego
D
Perini
Luca
L
Restelli
Ilaria
I
Binetti
Giuliano
G
Cappa
Stefano
S
Mariani
Claudio
C
Bresolin
Nereo
N
Scarpini
Elio
E
D000368:Aged; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000134:cerebrospinal fluid* / Q000235:genetics*; D004252:DNA Mutational Analysis; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000077153:Progranulins; D012737:Sex Factors
C111835:CCL2 protein, human; D018932:Chemokine CCL2; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins