| Summary: | Fibrinogen synthesis is stimulated by proinflammatory triggers and depends on α-, β- and γ-fibrinogen (<i>FGA</i>, <i>FGB</i>, <i>FGG</i>) genotypes. Constellations of fibrinogen, factor XIII A-subunit (<i>F13A</i>) and α<sub>2</sub>-antiplasmin (<i>A2AP</i>) genotypes predisposing for dense fibrin gels with high antifibrinolytic capacity (e.g., <i>FGB</i> rs1800790 A-allele carriage in <i>F13A</i> 34Val/Val or <i>A2AP</i> 6Arg/Arg wildtypes) are related with reduced inflammation. As both relationships are likely to influence each other, we tested whether the association of fibrinogen genotypes with fibrinogen levels is influenced by <i>F13A</i> and <i>A2AP</i> genotypes in a population under proinflammatory stress. In total, 639 women were followed during pregnancy (2218 observations). The relationship between fibrinogen genotypes and levels was statistically assessed in univariate and multivariate analyses without and with stratification for <i>F13A</i> Val34Leu and <i>A2AP</i> Arg6Trp. Strong associations with fibrinogen levels could be found for <i>FGB</i> rs1800790G > A, <i>FGA</i> rs2070016T > C and <i>FGG</i> rs1049636T > C. For <i>FGB</i> rs1800790G > A and <i>FGA</i> rs2070016T > C, this relationship significantly depended on <i>F13A</i> Val34Leu and <i>A2AP</i> Arg6Trp genotypes. Specifically, in <i>F13A</i> 34Val/Val wildtypes, carriage of <i>FGB</i> rs1800790A was related to significantly lower fibrinogen levels compared with <i>FGB</i> rs1800790GG wildtypes (<i>p</i> < 0.01). For <i>A2AP</i> 6Arg/Arg wildtypes, a comparable relationship could be found (<i>p</i> < 0.04). As these genotype constellations related to lower fibrinogen levels have previously been shown to be associated with reduced inflammatory activity, these findings suggest that the influence of fibrinogen, <i>F13A</i> and <i>A2AP</i> genotypes on inflammation could affect the control of fibrinogen levels and vice versa.
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