IL18 Haplotypes Are Associated with Serum IL-18 Concentrations in a Population-Based Study and a Cohort of Individuals with Premature Coronary Heart Disease
Open Access
- 1 December 2007
- journal article
- Published by Oxford University Press (OUP) in Clinical Chemistry
- Vol. 53 (12), 2078-2085
- https://doi.org/10.1373/clinchem.2007.092692
Abstract
Background: Interleukin (IL)-18 is a proinflammatory cytokine that has been implicated in several diseases, including atherosclerosis, and increased circulating IL-18 concentrations increase risk of future coronary heart disease (CHD). We evaluated the effect of common variation within the IL18 gene on concentrations of circulating IL-18.Methods: We measured IL-18, by ELISA, in the population-based study group [Carotid Ultrasound Disease Assessment Study (CUDAS)] and a predominantly male cohort with premature cardiovascular disease [Carotid Ultrasound in Patients with Ischaemic Heart Disease (CUPID)]. Using a tagging single-nucleotide polymorphism (SNP) approach that captured >90% of genetic variation, we identified 4 common (>10%) haplotypes.Results: A common SNP was associated with differences in IL-18 concentrations; in CUDAS individuals carrying 2 copies of the rare allele, concentrations were 13% higher than in those with no copies (P = 0.002). Haplotypes were also associated with significant differences in IL-18 concentrations in CUDAS and CUPID. Haplotype GTATA (frequency 23%) was associated with significantly lower IL-18 than others. In CUDAS, those carrying 2 copies had IL-18 concentrations 15% lower than those carrying no copies (P = 0.002); in CUPID, the difference was 22% (P = 0.004). These associations remained significant after adjustment for age, sex, hypertension, HDL cholesterol, waist-to-hip ratio, and alcohol consumption. Despite being associated with differences in IL-18 concentrations, the haplotypes did not occur at different frequencies in those with or without carotid atherosclerotic plaques.Conclusions: Variation within IL18 affects IL-18 concentrations in healthy and diseased individuals and thus may influence the pathophysiology of plaques at all stages of CHD progression.Keywords
Funding Information
- British Heart Foundation (FS/04/039, 2000/015)
- National Health and Medical Research Council (211980)
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