Proinflammatory genetic profiles in subjects with history of ischemic stroke.
OBJECTIVE
Proinflammatory genetic profiles, resulting from the combination of single nucleotide polymorphisms in genes encoding inflammatory molecules, may contribute to the development and progression of cardiovascular diseases. We evaluated the association between history of ischemic stroke and genetic profiles determined by the synergistic effects of polymorphisms in genes encoding prototypical inflammatory proteins.


METHODS
The study included 237 individuals with history of ischemic stroke and 223 age-matched and gender-matched controls. The polymorphisms of the C-reactive protein (CRP), interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin (E-sel), and matrix metalloproteinase-3 (MMP-3) genes were studied.


RESULTS
IL-6 GG, IL-6 GC, MCP-1 GG, ICAM-1 EE, E-sel AA, and MMP-3 5A5A genotypes were significantly and independently associated with stroke history. The odds of stroke increased with the number of high-risk genotypes: carrying 1 proinflammatory gene variant conferred a risk of 3.3 (1.6 to 6.9), whereas individuals concomitantly carrying 2 and 3 proinflammatory gene variants had adjusted odds ratios of 21.0 (7.6 to 57.5) and 50.3 (10.2 to 248.1), respectively.


CONCLUSIONS
Proinflammatory genetic profiles are significantly more common in subjects with stroke history. Synergistic effects between proinflammatory genotypes might be potential markers for cerebrovascular diseases.
Laboratory of Vascular Biology and Genetics, . Gemelli University Hospital, Università Cattolica del Sacro Cuore, School of Medicine, Rome, Italy.
Andrea
A
Flex
Eleonora
E
Gaetani
Pierangelo
P
Papaleo
Giuseppe
G
Straface
Anna S
AS
Proia
Giovanni
G
Pecorini
Paolo
P
Tondi
Paolo
P
Pola
Roberto
R
Pola
D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000235:genetics; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics; D019040:E-Selectin / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics*; D018836:Inflammation Mediators / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019040:E-Selectin; D007155:Immunologic Factors; D018836:Inflammation Mediators; D015850:Interleukin-6; D008263:Macrophage Migration-Inhibitory Factors; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D019278:Matrix Metalloproteinase 3