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


CONCLUSIONS
In healthy men, fibrinogen haplotypes are associated with serum IL-6 concentrations in a manner consistent with their impact on MI risk.
Mannila
M N
MN
Department of Medicine, Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska University Hospital, Solna, Sweden. maria.nastase.mannila@ki.se
Eriksson
P
P
Leander
K
K
Wiman
B
B
de Faire
U
U
Hamsten
A
A
Silveira
A
A
D000368:Aged; D001483:Base Sequence; D001777:Blood Coagulation / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005340:Fibrinogen / Q000032:analysis / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000097:blood* / Q000235:genetics* / Q000276:immunology
D015850:Interleukin-6; D005340:Fibrinogen