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 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.


RESULTS
We identified a C(-260)-->T nucleotide change, creating a HaeIII 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.
Hubacek
J A
JA
Institute for Clinical and Experimental Medicine, Prague, Czech Republic. jaroslav.hubacek@medicon.cz
Rothe
G
G
Pit'ha
J
J
Skodová
Z
Z
Stanĕk
V
V
Poledne
R
R
Schmitz
G
G
D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D003596:Cytosine / Q000378:metabolism*; D017931:DNA Primers; D005838:Genotype; D016905:Gram-Negative Bacterial Infections / Q000150:complications* / Q000276:immunology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009203:Myocardial Infarction / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D013941:Thymine / Q000378:metabolism*
D017931:DNA Primers; D018950:Lipopolysaccharide Receptors; D003596:Cytosine; D013941:Thymine