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Olle Melander

Principal investigator

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

Author

  • Sandra Olsson
  • Lukas Holmegaard
  • Katarina Jood
  • Marketa Sjögren
  • Gunnar Engström
  • Håkan Lövkvist
  • Christian Blomstrand
  • Bo Norrving
  • Olle Melander
  • Arne Lindgren
  • Christina Jern

Summary, in English

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.)

Department/s

  • Cardiovascular Research - Hypertension
  • Cardiovascular Research - Epidemiology
  • Neurology, Lund
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
  • EpiHealth: Epidemiology for Health

Publishing year

2012

Language

English

Pages

2278-2278

Publication/Series

Stroke: a journal of cerebral circulation

Volume

43

Issue

9

Document type

Journal article

Publisher

American Heart Association

Topic

  • Neurology

Keywords

  • cytokine
  • functional outcome
  • IL1RN
  • inflammation
  • single nucleotide
  • polymorphism
  • stroke

Status

Published

Research group

  • Cardiovascular Research - Hypertension
  • Cardiovascular Research - Epidemiology

ISBN/ISSN/Other

  • ISSN: 1524-4628