Prognostic value of interleukin-1 receptor antagonist gene polymorphism and cytomegalovirus seroprevalence in patients with coronary artery disease.
BACKGROUND
Chronic inflammatory stimuli such as cytomegalovirus (CMV) infection and various genetic polymorphisms determining the inflammatory response are assumed to be important risk factors in atherosclerosis. We investigated whether patients with stable coronary artery disease (CAD) and homozygous for allele 2 of the interleukin 1 receptor antagonist (IL-1RA) gene and seropositive for CMV represent a group particular susceptible for recurrent cardiovascular events.


METHODS
In a series of 300 consecutive patients with angiographically defined CAD a prospective follow-up was conducted (mean age 57.9 years, median follow-up time 38.2 months).


RESULTS
No statistically significant relationship was found between CMV serostatus and IL-1RN*2 (alone or in combination) and risk for future cardiovascular events (CVE). The hazard ratio (HR) for a CVE given positive CMV-serology and IL-1RN*2 was 1.07 (95% confidence interval (CI) 0.32-3.72) in the fully adjusted model compared to seronegative CMV patients not carrying the IL-1RN*2 allele. In this prospective cohort study involving 300 patients with angiographically defined CAD at baseline, homozygosity for allele 2 of the IL-1 RA and seropositivity to CMV alone and in combination were not associated with an increased risk for cardiovascular events during follow-up; in addition, combination of the CMV-seropositivity and IL-1RN*2 allele were not associated with a proinflammatory response.


CONCLUSIONS
Our study suggests that seropositivity to CMV and IL-1RA*2 genotype alone or in combination might not be a strong risk factor for recurrent cardiovascular events in patients with manifest CAD, and is not associated with levels of established inflammatory markers.
Rothenbacher
Dietrich
D
Department of Epidemiology, The German Centre for Research on Ageing, University of Heidelberg, Germany. rothenbacher@dzfa.uni-heidelberg.de
Brenner
Hermann
H
Mertens
Thomas
T
Hoffmann
Michael M
MM
Hoffmeister
Albrecht
A
Koenig
Wolfgang
W
D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000235:genetics; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006720:Homozygote; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D012698:Serologic Tests; D012795:Sialoglycoproteins / Q000235:genetics*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins