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Background Studies on the relation between thrombin activatable fibrinolysis inhibitor (TAFI) and arterial thrombosis have produced conflicting results.TAFI regulates fibrinolysis, but other roles of this inhibitor, including anti-inflammatory properties, have also been demonstrated.Design and Methods We investigated the association between TAFI activity and the risk of myocardial infarction. Additionally, we studied the association of common single nucleotide polymorphisms in the TAFI gene with levels of the TAFI protein and risk of myocardial infarction.We included 554 men under 70 years old with a first myocardial infarction and 643 controls participating in the Study of Myocardial Infarctions Leiden (SMILE), a case-control study.Results We found odds ratios (95% confidence intervals) of a first myocardial infarction of 2.4 (1.6–3.6), 3.2 (2.1–4.7) and 3.4 (2.3–5.1) for subjects whose TAFI levels were in the third, second and first quartiles (lowest TAFI levels), respectively, compared with the fourth quartile, after adjusting for arterial disease risk factors. The rare -438A and 1040T alleles were associated with lower, and the rare 505G allele with higher TAFI levels than the common alleles. Carriers of the -438A allele had an increased risk of myocardial infarction (odds ratio 1.6 (1.0–2.5) for AA; odds ratio 1.2 (0.9–1.5) for AG compared with GG). The other single nucleotide polymorphisms were not associated with myocardial infarction.Conclusions Low TAFI activity levels are associated with increased risk of a first myocardial infarction in men. The results on the association between TAFI single nucleotide polymorphisms and myocardial infarction were inconsistent.

Background We recently reported the association between the Malmö sequence variant in F9 (rs6048) and deep vein thrombosis.Design and Methods We aimed to study whether the association between F9 Malmö and deep vein thrombosis is explained by linkage disequilibrium with nearby single-nucleotide polymorphisms, and whether the association is explained biologically by F9 Malmö affecting factor IX antigen levels or activation of factor IX. We investigated the association of F9 Malmö and 28 nearby single-nucleotide polymorphisms with deep vein thrombosis in men from two case-control studies, LETS (n=380) and MEGA (n=1,469). We assessed the association of F9 Malmö with factor IX antigen level in male control subjects from LETS (n=191) and two subsets of MEGA (n=823 and n=484) and the association with endogenous thrombin potential in LETS control men. We studied the association between F9 Malmö and factor IX activation peptide in 1,199 healthy middle-aged men from the NPHS-II cohort.Results In the combined LETS and MEGA studies, the odds ratio (95% confidence interval) for the G allele of F9 Malmö, compared with the A allele, was 0.80 (0.69–0.93). One single-nucleotide polymorphism in F9, rs422187, was strongly linked to F9 Malmö (r2=0.94) and was similarly associated with deep vein thrombosis. No other single-nucleotide polymorphism or haplotype tested was more strongly associated. Factor IX antigen level, factor IX activation peptide levels and endogenous thrombin potential did not differ between F9 Malmö genotypes.Conclusions The F9 Malmö sequence variant was the most strongly associated with deep vein thrombosis among common single-nucleotide polymorphisms in the region. However, the biological mechanism by which F9 Malmö affects risk remains unknown.