IL-18 gene polymorphism, cardiovascular mortality and coronary artery disease
Jussi A. Hernesniemi
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Tampere University Hospital, Centre for Laboratory Medicine, Tampere, Finland
Medical School, University of Tampere, Tampere, Finland
Equal contributions.
Search for more papers by this authorKaisa Anttila
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Tampere University Hospital, Centre for Laboratory Medicine, Tampere, Finland
Medical School, University of Tampere, Tampere, Finland
Equal contributions.
Search for more papers by this authorTuomo Nieminen
Medical School, University of Tampere, Tampere, Finland
Department of Pharmacological Sciences, Medical School, University of Tampere, Tampere, Finland
Search for more papers by this authorMika Kähönen
Medical School, University of Tampere, Tampere, Finland
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
Search for more papers by this authorNina Mononen
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Tampere University Hospital, Centre for Laboratory Medicine, Tampere, Finland
Medical School, University of Tampere, Tampere, Finland
Search for more papers by this authorKjell Nikus
Heart Centre, Department of Cardiology, Tampere University Hospital, Tampere, Finland
Search for more papers by this authorVäinö Turjanmaa
Medical School, University of Tampere, Tampere, Finland
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
Search for more papers by this authorJari Viik
Department of Biomedical Engineering, Tampere University of Technology, Tampere, Finland
Search for more papers by this authorRami Lehtinen
Medical School, University of Tampere, Tampere, Finland
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
Tampere Polytechnic, University of Applied Sciences, Tampere, Finland
Search for more papers by this authorTerho Lehtimäki
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Tampere University Hospital, Centre for Laboratory Medicine, Tampere, Finland
Medical School, University of Tampere, Tampere, Finland
Search for more papers by this authorJussi A. Hernesniemi
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Tampere University Hospital, Centre for Laboratory Medicine, Tampere, Finland
Medical School, University of Tampere, Tampere, Finland
Equal contributions.
Search for more papers by this authorKaisa Anttila
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Tampere University Hospital, Centre for Laboratory Medicine, Tampere, Finland
Medical School, University of Tampere, Tampere, Finland
Equal contributions.
Search for more papers by this authorTuomo Nieminen
Medical School, University of Tampere, Tampere, Finland
Department of Pharmacological Sciences, Medical School, University of Tampere, Tampere, Finland
Search for more papers by this authorMika Kähönen
Medical School, University of Tampere, Tampere, Finland
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
Search for more papers by this authorNina Mononen
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Tampere University Hospital, Centre for Laboratory Medicine, Tampere, Finland
Medical School, University of Tampere, Tampere, Finland
Search for more papers by this authorKjell Nikus
Heart Centre, Department of Cardiology, Tampere University Hospital, Tampere, Finland
Search for more papers by this authorVäinö Turjanmaa
Medical School, University of Tampere, Tampere, Finland
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
Search for more papers by this authorJari Viik
Department of Biomedical Engineering, Tampere University of Technology, Tampere, Finland
Search for more papers by this authorRami Lehtinen
Medical School, University of Tampere, Tampere, Finland
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
Tampere Polytechnic, University of Applied Sciences, Tampere, Finland
Search for more papers by this authorTerho Lehtimäki
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Tampere University Hospital, Centre for Laboratory Medicine, Tampere, Finland
Medical School, University of Tampere, Tampere, Finland
Search for more papers by this authorAbstract
Eur J Clin Invest 2010; 40 (11): 994–1001
Background Interleukin 18(IL-18) is a pro-atherosclerotic cytokine. Elevated IL-18 levels and the genetic variation of the IL-18 have been previously linked with acute coronary events and cardiovascular mortality among patients with coronary artery disease (CAD). We studied the possible association between the IL-18 gene polymorphism and cardiovascular mortality during follow-up among Finnish patients who had undergone a clinical exercise stress test, in addition to the possible effect on the expression of angiography-verified CAD.
Materials and methods A total of 2152 patients of the Finnish Cardiovascular Study (cohort study) were followed up for 6·3 years and cardiovascular mortality was recorded. Angiography was performed on 461 patients. Genotyping of five common single nucleotide polymorphisms (SNPs) of the IL-18 gene was performed using the 5′nuclease assay for allelic discrimination with the ABI Prism 7900HT Sequence Detection System.
Results Among the study population, IL-18 gene polymorphism did not associate with cardiovascular mortality. According to adjusted binary regression analysis, the male carriers of one major haplotype (the only ones carrying the t allele of the +127 C/t SNP) had a lower occurrence rate for significant CAD defined as > 50% stenosis in at least one of the main branches of the coronary arteries (OR 0·495, 95% CI 0·862–0·284, P = 0·041). No associations were observed among women. The sex-by-genotype interaction was significant (P = 0·033).
Conclusions The IL-18 gene was not found to associate significantly with mortality. Among patients who had coronary angiography, one major haplotype of the IL-18 gene has a gender-dependent different impact on the expression of CAD.
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