title: Genetic variation within the interleukin-1 gene cluster and ischemic stroke.
abstract: OBJECTIVE
  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-1α, interleukin-1β, 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 Malmö 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 Malmö 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.
  
  
  CONCLUSIONS
  This comprehensive study, based on a tagSNP approach and replication, presents support for the role of IL1RN in overall IS.
authors: Department of Clinical Genetics, Box 445, SE-40530 Gothenburg, Sweden. sandra.olsson@neuro.gu.se
authors: Sandra
authors: S
authors: Olsson
authors: Lukas
authors: L
authors: Holmegaard
authors: Katarina
authors: K
authors: Jood
authors: Marketa
authors: M
authors: Sjögren
authors: Gunnar
authors: G
authors: Engström
authors: Håkan
authors: H
authors: Lövkvist
authors: Christian
authors: C
authors: Blomstrand
authors: Bo
authors: B
authors: Norrving
authors: Olle
authors: O
authors: Melander
authors: Arne
authors: A
authors: Lindgren
authors: Christina
authors: C
authors: Jern
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics*; D053582:Interleukin-1alpha / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D017472:Receptors, Interleukin-1 / Q000235:genetics; D020127:Recovery of Function; D020521:Stroke / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1