Association of RANTES G-403A gene polymorphism with increased risk of coronary arteriosclerosis.
OBJECTIVE
Polymorphisms in the RANTES (G-403A), monocyte chemoattractant protein-1 (MCP-1; A-2518G), stromal cell-derived factor-1beta (SDF-1beta; G801A), and C-C chemokine receptor-5 (CCR5; Delta32) genes have been associated with functional effects. These chemokines have been implicated in leucocyte recruitment to arterial lesions. In a case-control study, we explored relations between these polymorphisms and coronary artery disease (CAD), with respect to angiographic abnormalities and acute coronary syndromes (ACS).


RESULTS
The LUdwigshafen Risk and Cardiovascular health (LURIC) cohort was genotyped by RFLP-PCR. Based on coronary angiography, individuals were sub-divided into CAD cases (n = 2694) and controls (n = 530). RANTES-403 genotype frequencies were significantly different in cases and controls (chi2 = 4.17, p = 0.041), as were A allele carrier frequencies (36.01% vs. 30.19%, OR = 1.30 [95%-CI = 1.06-1.60], p = 0.010). By multivariate analysis, RANTES A-403 retained significant association with CAD (chi2 = 8.40, p = 0.0038). RANTES A-403 was associated with increased ACS prevalence (OR = 1.36 [95%-CI = 1.08-1.71], p = 0.0073). MCP-1 G-2518, SDF-1beta A801, and CCR5 Delta32 were not associated with CAD.


CONCLUSIONS
RANTES A-403 was associated with CAD independently from conventional risk factors and CRP or fibrinogen as inflammatory biomarkers. The association was enhanced in smokers and ACS, conditions where platelet activation and inflammation predominate. RANTES A-403 may increase genetic susceptibility to CAD.
Division of Cardiology, University of Lausanne, Switzerland.
Eleonora
E
Simeoni
Bernhard R
BR
Winkelmann
Michael M
MM
Hoffmann
Sylvain
S
Fleury
Juan
J
Ruiz
Lukas
L
Kappenberger
Winfried
W
März
Giuseppe
G
Vassalli
D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000235:genetics*; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
D018946:Chemokine CCL5