C(−260)→T Polymorphism in the Promoter of the CD14 Monocyte Receptor Gene as a Risk Factor for Myocardial Infarction

Abstract

Background —The CD14 receptor of monocytes is an important mediator for the activation of monocytes/macrophages by endotoxins from the envelope of Gram-negative bacteria (lipopolysaccharides). We identified a polymorphism in the CD14 receptor and examined whether this genetic marker influenced the expression of the CD14 receptor on monocytes and affected the predisposition to myocardial infarction. Methods and Results —We identified a C(−260)→T nucleotide change, creating a Hae III polymorphism in the promoter of the CD14 gene. The polymorphism was determined in 178 male patients <65 years old (cases; average age, 55.9±6.3 years) at the time of their first myocardial infarction and in 135 representative selected male control subjects (controls; average age, 55.2±11.5 years). The frequency of the T allele (absence of the cutting site) was 0.49 in cases and 0.35 in controls ( P =0.0005; OR, 1.781; 95% CI, 1.286 to 2.465). Subsequently, we measured the expression of monocyte CD14 by flow cytometry in 18 volunteers with different CD14 genotypes. A significantly higher density of the CD14 receptor was shown in the T/T homozygotes than in the others ( P =0.0028). Conclusions —A higher frequency of allele T(−260) in the promoter of the CD14 receptor gene was found in myocardial infarction survivors than in controls. At the same time, this variation was associated with a higher density of CD14 receptors in healthy volunteers. Therefore, we can conclude that in addition to the well-established risk factors, a genetically determined reaction of monocytes/macrophages to infectious stimuli could play an important role in the process of atherosclerosis.