Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: an observational study

• Published in: Cardiovascular diabetology 2011-12, Vol.10 (1), p.110-110
• Main Authors: Opstad, Trine B, Pettersen, Alf Å, Arnesen, Harald, Seljeflot, Ingebjørg
• Format: Article
• Language: English
• Subjects: Adult; Aged; Cardiovascular disease; Case-Control Studies; Coronary Artery Disease - blood; Coronary Artery Disease - complications; Coronary Artery Disease - genetics; Custom design; Deoxyribonucleic acid; Diabetes Complications - blood; Diabetes Complications - genetics; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; diabetes type 2; DNA; Female; Gene expression; Gene Frequency; Genetic Association Studies; Genotype & phenotype; Heart attacks; Hospitals; Humans; Hypertension; IL-18 mRNA; Intercellular Signaling Peptides and Proteins - blood; Interleukin-18 - blood; Interleukin-18 - genetics; Male; metabolic syndrome; Metabolic Syndrome - blood; Metabolic Syndrome - complications; Metabolic Syndrome - genetics; Middle Aged; Original Investigation; Polymorphism, Single Nucleotide; RNA, Messenger - blood; RNA, Messenger - genetics; Signal transduction; Single nucleotide polymorphisms; Studies
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/1475-2840-10-110

Increased IL-18 serum levels have been associated with diabetes type 2, metabolic syndrome and the severity of atherosclerosis. The present study investigated the presence and influence of IL-18 genetic variants on gene- and protein expression in stable coronary artery disease (CAD) patients. The +183 A/G (rs 5744292), -137 G/C (rs 187238) and -607 C/A (rs 1946518) polymorphisms were determined in 1001 patients with angiographically verified stable CAD, and in 204 healthy controls. IL-18 gene-expression was measured in circulating leukocytes in 240 randomly selected patients. Circulating IL-18 and IL-18 binding protein levels were measured immunologically in all patients. The +183 G-allele associated significantly with lower serum levels of IL-18 (p = 0.002, adjusted for age, glucose, body mass index and gender) and a 1.13- fold higher IL-18 gene-expression (p = 0.010). No influence was observed for the -137 G/C and -607 C/A polymorphisms. The IL-18 binding protein levels were not influenced by IL-18 genotypes. IL-18 levels were significantly higher in men as compared to women, and in patients with diabetes type 2 and metabolic syndrome compared to those without (p ≤ 0.001, all). The reduction in IL-18 levels according to the +183 G-allele was 3-4 fold more pronounced in diabetes and metabolic syndrome as compared to unaffected patients.Finally, the +183 AA genotype was more frequent in patients with hypertension (p = 0.042, adjusted for age, body mass index and gender). The reduction in serum IL-18 levels across increasing numbers of +183 G-alleles was especially apparent in patient with diabetes type 2 and metabolic syndrome, suggesting a beneficial GG genotype in relation to cardiovascular outcome in these patients. ClinicalTrials.gov: NCT00222261.