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

• 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.)

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)