The ABO Locus is Associated with Increased Fibrin Network Formation in Patients with Stable Coronary Artery Disease

Abstract

Abstract Background The ABO locus has been associated with increased risk of myocardial infarction (MI) in patients with coronary artery disease (CAD), but the underlying mechanisms are unknown. As altered fibrin clot structure has been demonstrated to predict MI in CAD patients, we examined the association between the ABO risk variant and fibrin clot properties, and investigated the effects of other CAD-associated risk variants. Methods We included 773 stable CAD patients. Patients were genotyped for 45 genome-wide CAD risk variants, including rs495828 at the ABO locus. We used a genetic risk score (GRS) for CAD calculated as the weighted sum of the number of risk alleles based on all 45 variants. Fibrin clot properties were evaluated using a turbidimetric assay. We studied clot maximum absorbance, a measure of clot density and fiber thickness, together with clot lysis time, an indicator of fibrinolysis potential. Results The rs495828 risk allele was present in 13.2% of patients and associated with higher clot maximum absorbance (adjusted effect size per risk allele: 1.05 [1.01 − 1.09], p = 0.01) but not with clot lysis time (p = 0.97). The rs12936587 (p = 0.04), rs4773144 (p = 0.02), and rs501120 (p = 0.04) were associated with clot lysis time; however, after Bonferroni correction, no significant associations were found between any of the remaining 44 CAD-associated variants and fibrin clot properties. The GRS was not associated with fibrin clot properties (p-values > 0.05). Conclusion The ABO risk allele was associated with a more compact fibrin network in stable CAD patients, which may represent a mechanism for increased MI risk in ABO risk variant carriers.