The association between fibrinogen haplotypes and myocardial infarction in men is partly mediated through pleiotropic effects on the serum IL-6 concentration

  • Mannila M
  • Eriksson P
  • Leander K
 et al. 
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Abstract

BACKGROUND AND OBJECTIVES: Fibrinogen haplotypes have been associated with risk of myocardial infarction (MI), independently of plasma fibrinogen concentration, and experimental data indicate that fibrinogen exerts pleiotropic effects on interleukin 6 (IL-6) production. Also, the coagulation factor XIII (gene symbol F13A1) Val34Leu haplotype tag single nucleotide polymorphism (htSNP) has been reported to exert pleiotropic effects on serum IL-6 concentration and to be associated with risk of MI. Therefore, in the present case-control study (a substudy to the Stockholm Heart Epidemiology Program), the effects of the fibrinogen gamma (FGG) 9340T>C [rs1049636], fibrinogen alpha (FGA) 2224G>A [rs2070011] and F13A1 Val34Leu [rs5985] htSNPs on concentrations of plasma fibrinogen and serum IL-6 and risk of MI were assessed. RESULTS: There were no associations between these SNPs and the plasma fibrinogen concentration. In contrast, in male controls the FGA 2224G>A htSNP was significantly associated with serum IL-6 concentration (P < 0.05). Also, in men the FGG-FGA*1 haplotype (containing the major FGG 9340T and FGA 2224G alleles) was associated with increased risk of MI [adjusted odds ratio (OR) 95% confidence interval (CI): 1.29 (1.02, 1.62)] and with higher IL-6 concentrations, whereas the least common FGG-FGA*4 haplotype (containing the minor FGG 9340C and FGA 2224A alleles) conferred lowered risk [adjusted OR (95% CI): 0.70 (0.57, 0.86)] and lowered IL-6 concentrations. In women, fibrinogen haplotypes were not associated with risk of MI after adjusting for cardiovascular risk factors. CONCLUSION: In healthy men, fibrinogen haplotypes are associated with serum IL-6 concentrations in a manner consistent with their impact on MI risk.

Author-supplied keywords

  • Fibrinogen
  • Haplotypes
  • Interleukin 6
  • Myocardial infarction
  • Pleiotropic effect

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Authors

  • M. N. Mannila

  • P. Eriksson

  • K. Leander

  • B. Wiman

  • U. De Faire

  • A. Hamsten

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