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Genetic variation within the interleukin-1 gene cluster and ischemic stroke
Sandra Olsson1, Lukas Holmegaard, Katarina Jood
1Department of Clinical Genetics, Box 445, SE-40530 Gothenburg, Sweden. sandra.olsson@neuro.gu.se
Stroke
|June 30, 2012
Summary
Genetic variations in the interleukin-1 receptor antagonist gene (IL1RN) are linked to ischemic stroke (IS). This study confirms IL1RN
Area of Science:
- Genetics
- Neuroscience
- Immunology
Background:
- Inflammation is increasingly recognized as a critical factor in the development of ischemic stroke (IS).
- Genetic predisposition may influence an individual's susceptibility to IS.
- Interleukin-1 (IL-1) pathway genes are implicated in inflammatory processes relevant to stroke.
Purpose of the Study:
- To investigate the association between genetic variations in IL1A, IL1B, and IL1RN genes and the risk of ischemic stroke (IS).
- To explore potential links between these genetic variations and specific etiologic subtypes of IS.
Main Methods:
- Analysis of twelve tag single nucleotide polymorphisms (tagSNPs) in IL1A, IL1B, and IL1RN.
- Utilized the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) cohort (844 IS patients, 668 controls).
- Replication analysis performed using the Lund Stroke Register and Malmö Diet and Cancer study (3145 IS patients, 1793 controls).
Main Results:
- A significant association was found between the IL1RN single nucleotide polymorphism rs380092 and overall IS risk (OR=1.21, P=0.03), replicated across cohorts.
- Combined analysis of all samples confirmed the association (OR=1.12, P=0.03).
- Nominal associations with cryptogenic stroke were observed for three IL1RN SNPs, but did not withstand multiple testing correction; elevated IL-1 receptor antagonist levels were noted in cryptogenic stroke patients.
Conclusions:
- The study provides evidence supporting the involvement of the IL1RN gene in the overall risk of ischemic stroke.
- Genetic variations in IL1RN may contribute to the pathophysiology of IS.
- Further research into the IL-1 pathway's role in stroke is warranted.
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