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IL18 haplotypes are associated with serum IL-18 concentrations in a population-based study and a cohort of individuals with premature coronary heart disease

Thompson, SR; McCaskie, PA; Beilby, JP; Hung, J; Jennens, M; Chapman, C; ... Humphries, SE; + view all (2007) IL18 haplotypes are associated with serum IL-18 concentrations in a population-based study and a cohort of individuals with premature coronary heart disease. CLIN CHEM , 53 (12) 2078 - 2085. 10.1373/clinchem.2007.092692.

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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. (C) 2007 American Association for Clinical Chemistry.

Type:Article
Title:IL18 haplotypes are associated with serum IL-18 concentrations in a population-based study and a cohort of individuals with premature coronary heart disease
DOI:10.1373/clinchem.2007.092692
Keywords:INTERLEUKIN-18 BINDING-PROTEIN, MYOCARDIAL-INFARCTION, IFN-GAMMA, LINKAGE DISEQUILIBRIUM, T-CELLS, RISK, ATHEROSCLEROSIS, EXPRESSION, GENE, POLYMORPHISM
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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