Summary

An intricate interplay between the genes encoding fibrinogengamma (FGG), alpha (FGA) and beta (FGB), coagulation factorXIII (F13A1) and interleukin 6 (IL6) and environmental factors islikely to influence plasma fibrinogen concentration, fibrin clotstructure and risk of myocardial infarction (MI). In the presentstudy, the potential contribution of SNPs harboured in the fibrinogen,IL6 and F13A1 genes to these biochemical and clinicalphenotypes was examined. A database and biobank based on387 survivors of a first MI and population-based controls wereused. Sixty controls were selected according to FGG 9340T>C[rs1049636] genotype for studies on fibrin clot structure usingthe liquid permeation method. The multifactor dimensionalityreduction method was used for interaction analyses. We herereport that the FGA 2224G>A [rs2070011] SNP (9.2%), plasmafibrinogen concentration (13.1%) and age (8.1%) appeared as in dependent determinants of fibrin gel porosity. The FGA2224G>A SNP modulated the relation between plasma fibrinogenconcentration and fibrin clot porosity.The FGG-FGA*4 haplotype,composed of the minor FGG 9340C and FGA 2224A alleles,had similar effects, supporting its reported protective rolein relation to MI. Significant epistasis on plasma fibrinogen concentrationwas detected between the FGA 2224G>A andF13A1 Val34Leu [rs5985] SNPs (p<0.001).The FGG 9340T>Cand FGB 1038G>A [rs1800791] SNPs appeared to interact onMI risk, explaining the association of FGG-FGB haplotypes withMI in the absence of effects of individual SNPs.Thus,epistatic andpleiotropic effects of polymorphisms contribute to the variationin plasma fibrinogen concentration, fibrin clot structure and riskof MI.