Monocyte chemoattractant protein-1 (MCP-1) gene polymorphism and risk of Alzheimer's disease in Italians.
Monocyte chemoattractant protein-1 (MCP-1) is a key molecule for monocyte chemotaxis and tissue extravasation and for the modulation of leukocyte function during inflammation. Upregulation of MCP-1 may occur in the brain of subjects affected by Alzheimer's disease (AD) and MCP-1 levels in plasma and cerebrospinal fluid have been proposed as biological markers for the inflammatory process that accompanies AD pathogenesis. Importantly, serum levels and biological activity of MCP-1 protein are strongly influenced by a single nucleotide polymorphism occurring at position -2518 of the MCP-1 gene promoter. A recent study has investigated the possible association between this gene polymorphism and AD in a Spanish population, with negative results. Here, we performed a case-control study to test whether the risk for AD might be influenced by the -2518 A/G polymorphism of the MCP-1 gene in an ethnically homogeneous Italian population. The GG genotype and the G allele of the MCP-1 gene polymorphism were significantly more common in the AD group than in control individuals (P<0.0001) A logistic regression analysis indicated that the GG genotype was an independent risk factor for AD in our population. This effect was not influenced by the presence of the APOE 4 high-risk allele, nor by the presence of other gene variations associated with a pro-inflammatory phenotype. These findings indicate that the -2518 A/G polymorphism of the MCP-1 gene is associated with AD in Italians and confirm that inflammatory gene variations may be important contributors in the development and progression of neurodegenerative disorders.
Pola
Roberto
R
Laboratory of Vascular Biology and Genetics, Department of Medicine, A. Gemelli University Hospital, Università Cattolica del Sacro Cuore School of Medicine, Rome, Italy. rob_pola@hotmail.com
Flex
Andrea
A
Gaetani
Eleonora
E
Proia
Anna S
AS
Papaleo
Pierangelo
P
Di Giorgio
Angela
A
Straface
Giuseppe
G
Pecorini
Giovanni
G
Serricchio
Michele
M
Pola
Paolo
P
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007558:Italy; D016015:Logistic Models; D008297:Male; D011110:Polymorphism, Genetic
D001057:Apolipoproteins E; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D018799:Intercellular Adhesion Molecule-1