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(Circulation. 1999;99:3210-3212.)
© 1999 American Heart Association, Inc.

Editorials

Polymorphism of the Lipopolysaccharide Receptor (CD14) and Myocardial Infarction

New Evidence for a Role of Gram-Negative Bacterial Infection?

John P. Kane, MD, PhD; Richard J. Havel, MD

From the University of California, San Francisco.

Correspondence to Richard J. Havel, MD, University of California, San Francisco, Box 0130, 505 Parnassus Ave, L-1337, San Francisco, CA 94143-0130.

Key Words: Editorials • genetics • myocardial infarction • epidemiology • immune system

Strong familial aggregation of coronary artery disease has long been recognized. Some of the increment of familial risk is attributable to established risk factors, such as plasma lipid levels, hypertension, smoking, and diabetes. Statistical regression studies, however, suggest that only 30% to 50% of the observed increment of coronary disease risk associated with a positive family history can be accounted for by canonical risk factors.^{1 2} Thus, significant factors remain to be discovered. These may involve retrieval of lipids from plaque, antioxidant defenses, endothelial dysfunction, abnormalities of platelet function, thrombogenesis and thrombolysis, and hereditary determinants of the inflammatory components of atherogenesis, among others.³

The idea that an inflammatory response directed at microorganisms might contribute to the atherogenic process is not new. In the last century, Virchow⁴ noted histopathological parallels between bacterial infection and atheromata. Recent reports have rekindled interest in the possibility that infection, particularly by Gram-negative bacteria, may contribute to the inflammatory component of atherosclerosis (including the major acute event of myocardial infarction) and that activation of monocytes may contribute to myocardial infarction as well as atherogenesis. Two European groups have now independently tested the hypothesis that genetic variations in the receptor for lipopolysaccharides (LPSs; endotoxins) produced by Gram-negative bacteria, CD14, may be a risk factor for myocardial infarction. Each group, one from Germany and the other from the Czech Republic, found a common polymorphism in the upstream, untranslated region of the CD14 gene. At the polymorphic site, cytosine or thymine is at position -260, within the Spl transcription factor . . . [Full Text of this Article]

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