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

  1. Rodrig Marculescu1,
  2. Georg Endler1,
  3. Martin Schillinger2,
  4. Nelly Iordanova3,
  5. Markus Exner1,
  6. Evelyn Hayden4,
  7. Kurt Huber3,
  8. Oswald Wagner1 and
  9. Christine Mannhalter1
  1. 1Department of Laboratory Medicine, School of Medicine, University of Vienna, Vienna, Austria
  2. 2Department of Internal Medicine II, Division of Angiology, School of Medicine, University of Vienna, Vienna, Austria
  3. 3Department of Internal Medicine II, Division of Cardiology, School of Medicine, University of Vienna, Vienna, Austria
  4. 4Department 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.

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