Interaction between the C-260T polymorphism of the CD14 gene and the plasma IL-6 concentration on the risk of myocardial infarction: the HIFMECH study
Autor: | Morange, P.E., Saut, N., Alessi, M.C., Frere, C., Hawe, E., Yudkin, J.S., Tremoli, E., Margaglione, M., Di Minno, G., Hamsten, A., Humphries, S.E., Juhan Vague, I., HIFMECH Study Group |
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Přispěvatelé: | Morange, Pe, Saut, N, Alessi, Mc, Frere, C, Hawe, E, Yudkin, J, Tremoli, E, Margaglione, M, DI MINNO, Giovanni, Hamsten, A, Humphries, Se, Juhan Vague, I, HIFMECH Study, Group |
Rok vydání: | 2005 |
Předmět: |
Male
medicine.medical_specialty Genotype Arteriosclerosis CD14 Lipopolysaccharide Receptors Pathogenesis myocardial infarction immune system inflammation Risk Factors Internal medicine medicine Humans Genetic Predisposition to Disease Myocardial infarction Allele Promoter Regions Genetic Interleukin 6 Polymorphism Genetic biology Interleukin-6 business.industry C-reactive protein Case-control study Middle Aged medicine.disease Endocrinology Case-Control Studies biology.protein Settore BIO/14 - Farmacologia Cardiology and Cardiovascular Medicine business |
Popis: | Experimental and clinical observations suggest that innate immunity plays a major role in the pathogenesis and progression of atherosclerosis. A common C-260T polymorphism in the promoter of the CD14 gene, the trans-membrane receptor of lipopolysaccharides, has been inconsistently associated with coronary heart disease. Our objective was to evaluate the contribution of the CD14 polymorphism to the inflammatory response and to the risk of myocardial infarction (MI). We used an European case-control study, the HIFMECH study, comparing 533 men with MI and 575 sex- and age-matched controls. Associations between genotype and disease outcome, according to interleukin-6 (IL-6) and C-reactive protein (CRP) levels, were assessed using conditional logistic regression. The CD14/C-260T polymorphism was associated with plasma IL-6 levels, T/T subjects having higher plasma levels than C/C in cases but not in controls (mean ± S.D.: 2.04 ± 1.37 versus 1.70 ± 1.15, p = 0.01; 1.20 ± 0.75 versus 1.35 ± 0.88, p = 0.31, respectively). Overall, the CD14/C-260T polymorphism was not associated with the risk of MI. However, in individuals with IL-6 plasma levels in the highest tertile, T allele carriers had a higher risk of MI than C/C (OR: 1.85; CI 95 1.05–3.25). IL-6 increased the risk of MI in carriers of the T allele (OR for first versus third IL-6 tertile: 4.02; CI 95 2.24–7.21), but not in C/C (OR: 0.75; CI 95 0.32–1.74, p = 0.004 for interaction). The data indicate a role for CD14/C-260T in MI. The risk mediated by the polymorphism is highly dependent on IL-6 plasma levels. © 2004 Published by Elsevier Ireland Ltd. |
Databáze: | OpenAIRE |
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