BACKGROUND: Acute coronary syndromes (ACS) and chronic stable angina represent extremes of the clinical spectrum of coronary artery disease (CAD). It is unknown whether genetic determinants affect the first clinical manifestation of CAD. We evaluated the role of the C(-260)T polymorphism in the promoter of the CD14-receptor gene, an important mediator of the inflammatory response to lipopolysaccharide. METHODS AND RESULTS: CD14 C(-260)T polymorphism was assessed in 100 patients with an acute presentation of CAD (group 1), 66 patients with stable presentation (group 2) and 88 healthy people (group 3); all patients were whites. In addition, baseline sCD14 plasma levels, and interleukin-6 production by circulating monocytes after in-vitro stimulation with lipopolysaccharide (1 ng/ml) were assessed. T/T homozygosis was more frequent in group 1 (36%, P < 0.001 versus others). Interleukin-6 production was higher in T/T homozygotes (median 4092.4; range 387-10 582 pg/ml) than in C/T heterozygotes (median 2442, range 40.5-9625 pg/ml, P < 0.001) and C/C homozygotes (median 3277.5; range 374.4-6250 pg/ml, P < 0.001). At multivariate analysis, T/T homozygosis and interleukin-6 production were independent predictors of acute presentation of CAD. CONCLUSION: The present study shows that genetic factors that influence the reactivity of inflammatory cells may play a role in determining the first clinical presentation of CAD.
BACKGROUND: Acute coronary syndromes (ACS) and chronic stable angina represent extremes of the clinical spectrum of coronary artery disease (CAD). It is unknown whether genetic determinants affect the first clinical manifestation of CAD. We evaluated the role of the C(-260)T polymorphism in the promoter of the CD14-receptor gene, an important mediator of the inflammatory response to lipopolysaccharide. METHODS AND RESULTS:CD14 C(-260)T polymorphism was assessed in 100 patients with an acute presentation of CAD (group 1), 66 patients with stable presentation (group 2) and 88 healthy people (group 3); all patients were whites. In addition, baseline sCD14 plasma levels, and interleukin-6 production by circulating monocytes after in-vitro stimulation with lipopolysaccharide (1 ng/ml) were assessed. T/T homozygosis was more frequent in group 1 (36%, P < 0.001 versus others). Interleukin-6 production was higher in T/T homozygotes (median 4092.4; range 387-10 582 pg/ml) than in C/T heterozygotes (median 2442, range 40.5-9625 pg/ml, P < 0.001) and C/C homozygotes (median 3277.5; range 374.4-6250 pg/ml, P < 0.001). At multivariate analysis, T/T homozygosis and interleukin-6 production were independent predictors of acute presentation of CAD. CONCLUSION: The present study shows that genetic factors that influence the reactivity of inflammatory cells may play a role in determining the first clinical presentation of CAD.