AIMS: 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). METHODS AND 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.
AIMS: 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). METHODS AND 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 CCR5Delta32 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.
Authors: Diederik F van Wijk; Sander I van Leuven; Manjinder S Sandhu; Michael W Tanck; Barbara A Hutten; Nicholas J Wareham; John J P Kastelein; Erik S G Stroes; Kay-Tee Khaw; S Matthijs Boekholdt Journal: Arterioscler Thromb Vasc Biol Date: 2010-04-29 Impact factor: 8.311
Authors: Friso L H Muntinghe; Marion Verduijn; Mike W Zuurman; Diana C Grootendorst; Juan Jesus Carrero; Abdul Rashid Qureshi; Karin Luttropp; Louise Nordfors; Bengt Lindholm; Vincent Brandenburg; Martin Schalling; Peter Stenvinkel; Elisabeth W Boeschoten; Raymond T Krediet; Gerjan Navis; Friedo W Dekker Journal: J Am Soc Nephrol Date: 2009-04-23 Impact factor: 10.121
Authors: Iris Steinbrugger; Anton Haas; Richard Maier; Wilfried Renner; Monika Mayer; Christoph Werner; Andreas Wedrich; Yosuf El-Shabrawi; Otto Schmut; Martin Weger Journal: Mol Vis Date: 2009-03-27 Impact factor: 2.367
Authors: Maria Bucova; Jan Lietava; Peter Penz; Frantisek Mrazek; Jana Petrkova; Marian Bernadic; Martin Petrek Journal: Mediators Inflamm Date: 2009-07-22 Impact factor: 4.711