Interleukin-1 Receptor Antagonist Genotype Is Associated With Coronary Atherosclerosis in Patients With Type 2 Diabetes
- Rodrig Marculescu1,
- Georg Endler1,
- Martin Schillinger2,
- Nelly Iordanova3,
- Markus Exner1,
- Evelyn Hayden4,
- Kurt Huber3,
- Oswald Wagner1 and
- Christine Mannhalter1
- 1Department of Laboratory Medicine, School of Medicine, University of Vienna, Vienna, Austria
- 2Department of Internal Medicine II, Division of Angiology, School of Medicine, University of Vienna, Vienna, Austria
- 3Department of Internal Medicine II, Division of Cardiology, School of Medicine, University of Vienna, Vienna, Austria
- 4Department of Business Administration, School of Business, Economics and Computer Science, University of Vienna, Vienna, Austria
Recently, inflammation has received considerable attention in the pathogenesis of both type 2 diabetes and atherosclerosis. The interleukin-1 receptor antagonist (IL-1ra) is a major modulator of the interleukin-1 pro-inflammatory pathway. We studied the relationship between a variable number tandem repeat (VNTR) polymorphism in intron 2 of the IL-1ra gene (IL1RN) and coronary artery disease (CAD) in patients with and without type 2 diabetes, following 787 consecutive patients admitted for suspected CAD. According to the current criteria of the American Diabetes Association, 250 patients had type 2 diabetes. In this group of patients, allele 2 carriers (n = 108) had an increased prevalence of CAD compared with noncarriers (85.2 vs. 73.2%), a difference that remained significant in a multivariate logistic regression model (odds ratio 2.2, 95% CI 1.1–4.3, P = 0.02). No association of CAD with allele 2 carrier status was present among nondiabetic patients (n = 537). Enzyme-linked immunosorbent assays showed decreased baseline plasma levels of IL-1ra in patients with type 2 diabetes, which may in part explain the role of the IL1RN VNTR in these patients.
Address correspondence and reprint requests to Oswald Wagner, MD, Department of Laboratory Medicine, AKH-Wien, Waehringer Guertel 18-20, A-1090 Vienna, Austria. E-mail:.
Received for publication 20 November 2001 and accepted in revised form 5 September 2002.
CAD, coronary artery disease; ELISA, enzyme-linked immunosorbent assay; FPG, fasting plasma glucose; IL-1, interleukin-1; IL-1ra, IL-1 receptor antagonist; IL1RN, IL-1ra gene; IQR, interquartile range; OR, odds ratio; VNTR, variable number tandem repeat.