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.
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
Roberto
R
Pola
Andrea
A
Flex
Eleonora
E
Gaetani
Anna S
AS
Proia
Pierangelo
P
Papaleo
Angela
A
Di Giorgio
Giuseppe
G
Straface
Giovanni
G
Pecorini
Michele
M
Serricchio
Paolo
P
Pola
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