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The ABO Locus is Associated with Increased Fibrin Network Formation in Patients with Stable Coronary Artery Disease
Anne Winther-Larsen1,2, Morten Krogh Christiansen3, Sanne Bøjet Larsen3
1Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
Insights
The ABO risk allele is linked to denser fibrin clots in coronary artery disease (CAD) patients, potentially explaining increased myocardial infarction (MI) risk. This study investigated ABO variants and fibrin clot properties in CAD.
Area of Science:
- Cardiovascular Genetics
- Thrombosis and Hemostasis
- Molecular Cardiology
Background:
- The ABO locus is associated with myocardial infarction (MI) risk in coronary artery disease (CAD) patients, but mechanisms remain unclear.
- Altered fibrin clot structure is a known predictor of MI in CAD patients.
- This study investigates the link between ABO risk variants and fibrin clot properties.
Purpose of the Study:
- To examine the association between the ABO risk variant and fibrin clot properties in stable CAD patients.
- To investigate the effects of other CAD-associated risk variants on fibrin clot properties.
Main Methods:
- Genotyping of 773 stable CAD patients for 45 genome-wide CAD risk variants, including the ABO locus variant rs495828.
- Calculation of a CAD genetic risk score (GRS) based on risk alleles.
- Evaluation of fibrin clot properties, including maximum absorbance (clot density/fiber thickness) and clot lysis time, using turbidimetric assays.
Main Results:
- The rs495828 risk allele was associated with significantly higher clot maximum absorbance (p=0.01), indicating a denser clot.
- No significant association was found between the ABO risk allele and clot lysis time (p=0.97).
- None of the other 44 CAD variants or the overall GRS showed significant associations with fibrin clot properties after Bonferroni correction.
Conclusions:
- The ABO risk allele is associated with a more compact fibrin network in stable CAD patients.
- This altered fibrin structure may represent a key mechanism contributing to the increased MI risk observed in carriers of ABO risk variants.
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.
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