OBJECTIVE: Inflammation plays a major role in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI). CD14 is the receptor for bacterial lipopolysaccharide in monocytes and mediates the production of proinflammatory cytokines. The promoter of the CD14 gene has a polymorphic site in position - 159 (C-->T) and T-homozygotes have been shown to express higher amounts of CD14 by some investigators. We and others have found an association of the T-allele with past MI in former studies, but reports in the literature are contradictory. METHODS AND RESULTS: We investigated a study group with an assumed high genetic risk by selecting 200 patients suffering from angiographically verified CAD or MI who were younger than 50 years or who had only one or no risk factor (hypertension, smoking, elevated body mass index, impaired glucose tolerance or elevated cholesterol levels). We used 252 healthy subjects as controls. Additionally, the levels of soluble (s) CD14 in plasma and amount of membranous (m) CD14 on the surface of monocytes were determined in different genotypes. We found no association of either genotype with CAD, extent of CAD, or a history of MI. No significant correlation was found after adjustment for vascular risk factors. In addition, no significant differences in the density of monocyte mCD14 or in plasma levels of sCD14 were detectable among the various genotypes. CONCLUSIONS: The assumed weak association of the TT-genotype of the CD14 promoter polymorphism with MI could not be not established in a well-defined group of young patients with a high genetic risk. The association of the polymorphism with expression of sCD14 or mCD14 was not confirmed. Georg Thieme Verlag KG Stuttgart. New York.
OBJECTIVE: Inflammation plays a major role in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI). CD14 is the receptor for bacterial lipopolysaccharide in monocytes and mediates the production of proinflammatory cytokines. The promoter of the CD14 gene has a polymorphic site in position - 159 (C-->T) and T-homozygotes have been shown to express higher amounts of CD14 by some investigators. We and others have found an association of the T-allele with past MI in former studies, but reports in the literature are contradictory. METHODS AND RESULTS: We investigated a study group with an assumed high genetic risk by selecting 200 patients suffering from angiographically verified CAD or MI who were younger than 50 years or who had only one or no risk factor (hypertension, smoking, elevated body mass index, impaired glucose tolerance or elevated cholesterol levels). We used 252 healthy subjects as controls. Additionally, the levels of soluble (s) CD14 in plasma and amount of membranous (m) CD14 on the surface of monocytes were determined in different genotypes. We found no association of either genotype with CAD, extent of CAD, or a history of MI. No significant correlation was found after adjustment for vascular risk factors. In addition, no significant differences in the density of monocyte mCD14 or in plasma levels of sCD14 were detectable among the various genotypes. CONCLUSIONS: The assumed weak association of the TT-genotype of the CD14 promoter polymorphism with MI could not be not established in a well-defined group of young patients with a high genetic risk. The association of the polymorphism with expression of sCD14 or mCD14 was not confirmed. Georg Thieme Verlag KG Stuttgart. New York.