C(-260)-> T polymorphism in the promoter of the CD14 monocyte receptor gene as a risk factor for myocardial infarction

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 t he CD14 receptor and examined whether this genetic marker influenced the ex pression 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 Haem 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 repr esentative 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 cy tometry in 18 volunteers with different CD14 genotypes. A significantly hig her density of the CD14 receptor was shown in the T/T homozygotes than in t he others (P=0.0028). Conclusions-A higher frequency of allele T(-260) in the promoter of the CD1 4 receptor gene was found in myocardial infarction survivors than in contro ls. At the same time, this variation was associated with a higher density o f CD14 receptors in healthy volunteers. Therefore, we can conclude that in addition to the well-established risk factors, a genetically determined rea ction of monocytes/macrophages to infectious stimuli could play an importan t role in the process of atherosclerosis.