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Genetic Variation Within the Interleukin-1 Gene Cluster and Ischemic Stroke

Journal article
Authors Sandra Olsson
Lukas Holmegaard
Katarina Jood
M. Sjogren
G. Engstrom
H. Lovkvist
Christian Blomstrand
B. Norrving
O. Melander
A. Lindgren
Christina Jern
Published in Stroke
Volume 43
Issue 9
Pages 2278-+
ISSN 0039-2499
Publication year 2012
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Pages 2278-+
Language en
Links dx.doi.org/10.1161/strokeaha.111.64...
https://gup.ub.gu.se/file/86201
Keywords cytokine, functional outcome, IL1RN, inflammation, single nucleotide polymorphism, stroke, c-reactive protein, receptor antagonist, myocardial-infarction, cerebral, infarction, inflammatory system, polymorphism -511, risk-factors, association, population, susceptibility, rkowski e, 1995, stroke, v26, p1393
Subject categories Neurosciences

Abstract

Background and Purpose-Evidence is emerging that inflammation plays a key role in the pathophysiology of ischemic stroke (IS). The aim of this study was to investigate whether genetic variation in the interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist genes (IL1A, IL1B, and IL1RN) is associated with IS and/or any etiologic subtype of IS. Methods-Twelve tagSNPs were analyzed in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), which comprises 844 patients with IS and 668 control subjects. IS subtypes were defined according to the Trial of Org 10172 in Acute Stroke Treatment criteria in SAHLSIS. The Lund Stroke Register and the Malmo Diet and Cancer study were used as a replication sample for overall IS (in total 3145 patients and 1793 control subjects). Results-The single nucleotide polymorphism rs380092 in IL1RN showed an association with overall IS in SAHLSIS (OR, 1.21; 95% CI, 1.02-1.43; P = 0.03), which was replicated in the Lund Stroke Register and the Malmo Diet and Cancer study sample. An association was also detected in all samples combined (OR, 1.12; 95% CI, 1.04 -1.21; P = 0.03). Three single nucleotide polymorphisms in IL1RN (including rs380092) were nominally associated with the subtype of cryptogenic stroke in SAHLSIS, but the statistical significance did not remain after correction for multiple testing. Furthermore, increased plasma levels of interleukin-1 receptor antagonist were observed in the subtype of cryptogenic stroke compared with controls. Conclusion-This comprehensive study, based on a tagSNP approach and replication, presents support for the role of IL1RN in overall IS. (Stroke. 2012; 43: 2278-2282.)

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