The Health Outcome
Coronary artery disease (CAD) is a leading cause of morbidity and mortality in the United States and other developed countries. Recent research has revealed that infectious agents and cytokines, by causing or mediating inflammatory processes in the vessel wall, may play a role in the pathogenesis of CAD. Several studies have evaluated Chlamydia pneumoniae, a common respiratory pathogen, as a risk factor for CAD; results of these studies, however, are conflicting. The cytokines, interleukin -1beta (IL-1B) and interleukin-1 receptor antagonist (IL-1Ra), may be involved in the development of CAD. Moreover, family history is a well-established risk factor for CAD, yet few associations between CAD and gene polymorphisms have been demonstrated. Research is currently focused on polymorphisms of the IL-1B and IL-1Ra genes as predictors of CAD development and as potential modifiers of inflammatory processes triggered by systemic infections.
The Finding
Momiyama and colleagues (1) conducted a study among Japanese men to elucidate the effects of IL-1B and IL-1Ra gene polymorphisms and Chlamydia pneumoniae (CP) infection on subjects at risk for coronary artery disease (CAD). A detailed abstraction of this article is available online as part of the HuGENet™ e-journal club (2). The authors found the prevalence of IL-1B C/C genotype and/or IL-1Ra 2-or 3-repeat allele to be significantly higher in patients with CAD then in patients without CAD. They also found a nearly three-fold increased CAD prevalence among patients with and without CP seropositivity (multivariate analysis). The prevalence of CP IgG seropositivity did not differ significantly between patients with and those without CAD. In an analysis of data stratified by the presence/absence of the IL-1 variants and by +/- CP seropositivity, the authors observed a stepwise increase in CAD prevalence, with the lowest CAD prevalence among patients without either factor and the highest prevalence among individuals with both factors. The authors report odds ratios for CAD of 1.4, in the group with seropositivity alone, 1.7 in the group with variants alone, and 3.8 in the group with seropositivity and variants.
The paper also addressed the association of IL-1 gene variants and CP infection with myocardial infarction (MI). The prevalence of MI was found to be significantly higher among patients with both CP seropositivity and the IL-1 gene variants than the prevalence among those in the other three groups. In a comparison of patients with both CP seropositivity and presence of the gene variants to those without either factor, the odds ratio was 2.7 and was statistically significant. After controlling for other known risk factors for coronary artery disease, the authors found a relationship between the IL-1 gene variants and MI only in patients with CP seropositivity.
Public Health Implications
These results, if true, suggest that polymorphisms in interleukin-1 genes may modify inflammatory responses to Chlamydia pneumoniae infection and may explain the reported individual differences in the atherogenic effects of CP infection. While this study and several others show the IL-1B and IL-Ra variants to be associated with CAD and MI, the functional effects and mechanisms of the polymorphisms remain unknown. The authors recognize that the study is limited as the data are cross-sectional and collected in a population of Japanese men with suspected CAD. Overall, the findings should be viewed as hypothesis-generating. These data require confirmation before recommendations can be made for using tests for IL-1 gene variants in clinical practice. The role of CP infection in the pathogenesis of vascular disease also remains undetermined and deserves careful evaluation in a prospective study.
References
- Momiyama Y, Hirano R, Taniguchi H, Nakamura H, Ohsuzu F. Effects of interleukin-1 gene polymorphisms on the development of coronary artery disease associated with Chlamydia pneumoniae infection. Journal of the American College of Cardiology 2001; 38(3):712-7
- E-journal club abstraction template
