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

Olsson, Sandra; Holmegaard, Lukas; Jood, Katarina; Sjögren, Marketa LU ; Engström, Gunnar LU ; Lövkvist, Håkan LU ; Blomstrand, Christian; Norrving, Bo LU ; Melander, Olle LU and Lindgren, Arne LU , et al. (2012) In Stroke: a journal of cerebral circulation 43(9). p.2278-2278
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... (More)
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.) (Less)
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Contribution to journal
publication status
published
subject
keywords
cytokine, functional outcome, IL1RN, inflammation, single nucleotide, polymorphism, stroke
in
Stroke: a journal of cerebral circulation
volume
43
issue
9
pages
2278 - 2278
publisher
American Heart Association
external identifiers
  • wos:000308416300017
  • scopus:84865588842
ISSN
1524-4628
DOI
10.1161/STROKEAHA.111.647446
language
English
LU publication?
yes
id
71caabde-bdb1-472d-a46a-28d0a1602fb7 (old id 3191397)
date added to LUP
2012-12-03 07:11:44
date last changed
2017-10-01 04:22:15
@article{71caabde-bdb1-472d-a46a-28d0a1602fb7,
  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.)},
  author       = {Olsson, Sandra and Holmegaard, Lukas and Jood, Katarina and Sjögren, Marketa and Engström, Gunnar and Lövkvist, Håkan and Blomstrand, Christian and Norrving, Bo and Melander, Olle and Lindgren, Arne and Jern, Christina},
  issn         = {1524-4628},
  keyword      = {cytokine,functional outcome,IL1RN,inflammation,single nucleotide,polymorphism,stroke},
  language     = {eng},
  number       = {9},
  pages        = {2278--2278},
  publisher    = {American Heart Association},
  series       = { Stroke: a journal of cerebral circulation},
  title        = {Genetic Variation Within the Interleukin-1 Gene Cluster and Ischemic Stroke},
  url          = {http://dx.doi.org/10.1161/STROKEAHA.111.647446},
  volume       = {43},
  year         = {2012},
}