Interleukin-1 Receptor Antagonist Genotype Is Associated With Coronary Atherosclerosis in Patients With Type 2 Diabetes

Interleukin-1 Receptor Antagonist Genotype Is Associated With Coronary Atherosclerosis in Patients With Type 2 Diabetes Rodrig Marculescu 1 , Georg Endler 1 , Martin Schillinger 2 , Nelly Iordanova 3 , Markus Exner 1 , Evelyn Hayden 4 , Kurt Huber 3 , Oswald Wagner 1 and Christine Mannhalter 1 1 Department of Laboratory Medicine, School of Medicine, University of Vienna, Vienna, Austria 2 Department of Internal Medicine II, Division of Angiology, School of Medicine, University of Vienna, Vienna, Austria 3 Department of Internal Medicine II, Division of Cardiology, School of Medicine, University of Vienna, Vienna, Austria 4 Department of Business Administration, School of Business, Economics and Computer Science, University of Vienna, Vienna, Austria Abstract 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. Footnotes 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: oswald.wagner{at}univie.ac.at . 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. DIABET