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

Cardiovascular Diabetology

Original Investigation

Trine B Opstad¹  Alf Å Pettersen¹  Harald Arnesen²  Ingebjørg Seljeflot² 

[1] Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital, Ulleval, Norway;Center for Heart Failure Research, Oslo University Hospital, Norway;Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital, Ulleval, Norway;Center for Heart Failure Research, Oslo University Hospital, Norway;Faculty of Medicine, University of Oslo, Norway;

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

DOI  :  10.1186/1475-2840-10-110

 received in 2011-10-20, accepted in 2011-12-05,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundIncreased 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.MethodsThe +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.ResultsThe +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).ConclusionThe 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 NumberClinicalTrials.gov: NCT00222261

【 授权许可】

CC BY   
© Opstad et al; licensee BioMed Central Ltd. 2011