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Open Access Original investigation

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

Trine B Opstad12*, Alf Å Pettersen12, Harald Arnesen123 and Ingebjørg Seljeflot123

Author Affiliations

1 Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital, Ulleval, Norway

2 Center for Heart Failure Research, Oslo University Hospital, Norway

3 Faculty of Medicine, University of Oslo, Norway

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Cardiovascular Diabetology 2011, 10:110  doi:10.1186/1475-2840-10-110

Published: 5 December 2011

Abstract

Background

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.

Methods

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.

Results

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).

Conclusion

The reduction in serum IL-18 levels across increasing numbers of +183G-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.

Clinical Trial Registration Number

ClinicalTrials.gov: NCT00222261

Keywords:
Single nucleotide polymorphisms; IL-18 mRNA; diabetes type 2; metabolic syndrome; hypertension