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The association between fibrinogen haplotypes and myocardial infarction in men is partly mediated through pleiotropic effects on the serum IL-6 concentration.
J Intern Med. 2007 Feb; 261(2):138-47.JI

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.

Authors+Show Affiliations

Department of Medicine, Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska University Hospital, Solna, Sweden. maria.nastase.mannila@ki.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17241179

Citation

Mannila, M N., et al. "The Association Between Fibrinogen Haplotypes and Myocardial Infarction in Men Is Partly Mediated Through Pleiotropic Effects On the Serum IL-6 Concentration." Journal of Internal Medicine, vol. 261, no. 2, 2007, pp. 138-47.
Mannila MN, Eriksson P, Leander K, et al. The association between fibrinogen haplotypes and myocardial infarction in men is partly mediated through pleiotropic effects on the serum IL-6 concentration. J Intern Med. 2007;261(2):138-47.
Mannila, M. N., Eriksson, P., Leander, K., Wiman, B., de Faire, U., Hamsten, A., & Silveira, A. (2007). The association between fibrinogen haplotypes and myocardial infarction in men is partly mediated through pleiotropic effects on the serum IL-6 concentration. Journal of Internal Medicine, 261(2), 138-47.
Mannila MN, et al. The Association Between Fibrinogen Haplotypes and Myocardial Infarction in Men Is Partly Mediated Through Pleiotropic Effects On the Serum IL-6 Concentration. J Intern Med. 2007;261(2):138-47. PubMed PMID: 17241179.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The association between fibrinogen haplotypes and myocardial infarction in men is partly mediated through pleiotropic effects on the serum IL-6 concentration. AU - Mannila,M N, AU - Eriksson,P, AU - Leander,K, AU - Wiman,B, AU - de Faire,U, AU - Hamsten,A, AU - Silveira,A, PY - 2007/1/24/pubmed PY - 2007/2/21/medline PY - 2007/1/24/entrez SP - 138 EP - 47 JF - Journal of internal medicine JO - J Intern Med VL - 261 IS - 2 N2 - 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. SN - 0954-6820 UR - https://www.unboundmedicine.com/medline/citation/17241179/The_association_between_fibrinogen_haplotypes_and_myocardial_infarction_in_men_is_partly_mediated_through_pleiotropic_effects_on_the_serum_IL_6_concentration_ DB - PRIME DP - Unbound Medicine ER -