A new promoter polymorphism in the gene of lipopolysaccharide receptor CD14 is associated with expired myocardial infarction in patients with low atherosclerotic risk profile

Recent findings suggest that inflammation plays a role in atherosclerosis a nd its acute complications. Cellular response in infections with Gram-negat ive bacteria is mediated by bacterial lipopolysaccharide (LPS), which activ ates monocytes to expression of cytokines, growth factors, and procoagulato ry factors via LPS receptor CD14. Endothelial cells and smooth muscle cells are stimulated by a complex of LPS and soluble CD14. In this study, LPS re ceptor CD14 was analyzed to find genetic variants and check them for an ass ociation with coronary artery disease or myocardial infarction (MI). When s creening the CD14 gene by single-strand conformation polymorphism analysis, a promoter polymorphism was detected and confirmed as a T-to-C exchange at position -159. We determined the genotypes of 2228 men who had undergone c oronary angiography for diagnostic purposes. Within the total study group t here was no significant association of either genotype with MI or coronary artery disease. However, in a subgroup with low coronary risk (normotensive nonsmokers), a relative risk for MI in probands homozygous for the T allel e could be evaluated (OR, 1.6; 95% CI, 1.0 to 2.4; P<0.05). The association was even stronger in low-risk patients older than 62 years (OR, 3.8; 95% C I, 1.6 to 9.0; P<0.01). In conclusion, we describe a new CD14 promoter poly morphism that is associated with MI, especially in older patients with a lo w atherosclerotic risk profile.