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

P. E. Morange, N. Saut, M. C. Alessi, C. Frere, E. Hawe, J. S. Yudkin, E. Tremoli, M. Margaglione, G. Di Minno, A. Hamsten, S. E. Humphries, I. Juhan-Vague

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)317-323
Number of pages7
JournalAtherosclerosis
Volume179
Issue number2
DOIs
Publication statusPublished - Apr 2005

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Interleukin-6
Myocardial Infarction
Genes
Alleles
CD14 Antigens
Innate Immunity
C-Reactive Protein
Coronary Disease
Case-Control Studies
Atherosclerosis
Logistic Models
Genotype
Membranes

Keywords

  • Immune system
  • Inflammation
  • Myocardial infarction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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. / 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.

In: Atherosclerosis, Vol. 179, No. 2, 04.2005, p. 317-323.

Research output: Contribution to journalArticle

Morange, PE, Saut, N, Alessi, MC, Frere, C, Hawe, E, Yudkin, JS, Tremoli, E, Margaglione, M, Di Minno, G, Hamsten, A, Humphries, SE & Juhan-Vague, I 2005, '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', Atherosclerosis, vol. 179, no. 2, pp. 317-323. https://doi.org/10.1016/j.atherosclerosis.2004.10.014
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. / 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. In: Atherosclerosis. 2005 ; Vol. 179, No. 2. pp. 317-323.
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abstract = "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.",
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AU - Saut, N.

AU - Alessi, M. C.

AU - Frere, C.

AU - Hawe, E.

AU - Yudkin, J. S.

AU - Tremoli, E.

AU - Margaglione, M.

AU - Di Minno, G.

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