Abstract TP114: Post-stroke Fatigue Is Linked To The IL1RN Polymorphism rs4251961

Background: Post-stroke fatigue (PSF) is common, but the biological basis of PSF is unknown. We explored the relationship between PSF, systemic inflammation and genetic polymorphisms that affect the immune response. Methods: In a substudy of a larger trial that evaluated the role of the immune response on stroke outcome, patients were asked about their level of fatigue at 30, 90, 180, and 365 days after ischemic stroke. (The degree fatigue of was quantified using the Fatigue Assessment Scale [FAS], with possible scores of 10 (minimal fatigue) to 50 (severe fatigue). Plasma cytokine concentrations were analyzed and patients genotyped for polymorphisms in the promoter of the interleukin-1 receptor antagonist (IL-1ra) gene (IL1RN; rs4251961). The minor allele (C) is associated with decreased IL-1ra in healthy adults in comparison with the major (T) allele. Results: Of patients for whom FAS scores were available (N=38), there were 16 (41%) with TT, 14 (36%) with CT and 8 (21%) with CC genotypes. The degree of fatigue (median [interquartile range]) was remarkably constant over time (22 [16, 29]) and tended to be higher in patients with a C allele (Figure). The FAS scores for patients with the minor C allele was 26 (17, 32) and was 18 in those without (13, 26; P=0.046). If fatigue is defined as an FAS score greater than the 75th percentile value for all patients (>29), 8/22 (36%) of patients with the C allele experienced fatigue while only 1/16 (6%) patients with TT did (P=0.031). Controlling for stroke severity, age and gender, the odds ratio (95% confidence interval) for developing fatigue (FAS>29) with a C allele was 9.96 (1.13-87.42; P=0.038). The concentration of IL-1ra did not differ among patients with the C allele and those without at any time point and was not associated with the FAS score. Conclusions: The rs4251961 polymorphism of IL1RN appears to be associated with PSF. This finding, and the relationship to systemic markers of inflammation, will need to be validated in a larger cohort.