Interleukin-1 receptor antagonist genotype is associated with coronary atherosclerosis in patients with type 2 diabetes.
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.
Marculescu
Rodrig
R
Department of Laboratory Medicine, School of Medicine, University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Endler
Georg
G
Schillinger
Martin
M
Iordanova
Nelly
N
Exner
Markus
M
Hayden
Evelyn
E
Huber
Kurt
K
Wagner
Oswald
O
Mannhalter
Christine
C
D000368:Aged; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D015995:Prevalence; D012795:Sialoglycoproteins / Q000097:blood / Q000235:genetics*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins