(Circulation. 1999;99:3218-3220.)
© 1999 American Heart Association, Inc.
Brief Rapid Communications |
C(-260)
T Polymorphism in the Promoter of the CD14 Monocyte Receptor Gene as a Risk Factor for Myocardial Infarction
k, MDFrom the Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Correspondence to Jaroslav A. Hubacek, Institute for Clinical and Experimental Medicine, Laboratory of Atherosclerosis Research, Vídenská 1958/9, Prague 4, Czech Republic 140 21. E-mail jaroslav.hubacek{at}medicon.cz
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 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.
Key Words: genetics • myocardial infarction • epidemiology • immune system
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