CLINICAL STUDY: CORONARY ARTERY DISEASE
Effects of interleukin-1 gene polymorphisms on the development of coronary artery disease associated with Chlamydia pneumoniae infection
Yukihiko Momiyama, MD*,
Reiko Hirano, PhD*,
Hiroaki Taniguchi, MD*,
Haruo Nakamura, MD and
Fumitaka Ohsuzu, MD*
* First Department of Internal Medicine, National Defense Medical College, Saitama, Japan
Mitsukoshi Health and Welfare Foundation, Tokyo, Japan
Manuscript received January 31, 2001;
revised manuscript received May 14, 2001,
accepted May 23, 2001.
Reprint requests and correspondence: Dr. Yukihiko Momiyama, First Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359–8513, Japan
momiyama{at}me.ndmc.ac.jp
OBJECTIVES
This study was done to elucidate the effects of interleukin (IL)-1 gene polymorphisms on coronary artery disease (CAD) associated with Chlamydia pneumoniae (CP) infection.
BACKGROUND
It was suggested that CP was associated with CAD. However, genetic factors involved in CAD associated with CP infection are unknown.
METHODS
We evaluated CP immunoglobulin G (IgG) seropositivity and IL-1ß (a C/T transition at –511) and IL-1 receptor antagonist (IL-1Ra) (a variable-number repeat in intron 2) gene polymorphisms in 292 patients undergoing coronary angiography.
RESULTS
Seropositivity for CP was present in 61% of patients with CAD versus 51% without CAD (p = NS). The percentage of patients having IL-1ß (–511) C/C genotype and/or IL-1Ra (intron 2) 2- or 3-repeat allele was higher in patients with CAD than without CAD (29 vs. 16%, p < 0.025). To clarify the effects of these CAD-associated variants (IL-1ß C/C and/or IL-1Ra 2- or 3-repeat), patients were divided into four groups. A stepwise increase in CAD prevalence was observed depending on CP seropositivity and the variants. Odds ratios (ORs) for CAD were 1.4 in the group with seropositivity alone, 1.7 with the variants alone and 3.8 with seropositivity and the variants. Such variants were associated with CAD in both patients with and without seropositivity. Interestingly, high prevalence of myocardial infarction (MI) was confined to the group with seropositivity and the variants (OR, 2.8). The variants were associated with MI only in patients with CP seropositivity.
CONCLUSIONS
The IL-1 gene polymorphisms were found to play a role in the development of CAD, especially MI, in patients with CP infection.
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Abbreviations and Acronyms
| | CAD | = coronary artery disease | | CI | = confidence interval | | CP | = Chlamydia pneumoniae | | ELISA | = enzyme-linked immunosorbent assay | | Ig | = immunoglobulin | | IL | = interleukin | | IL-1Ra | = interleukin-1 receptor antagonist | | MI | = myocardial infarction | | OR | = odds ratio | | PCR | = polymerase chain reaction |
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