Coagulation Factor XIII and Cardiovascular Disease in UK Asian Patients Undergoing Coronary Angiography

SummaryPossession of the coagulation factor XIII Val34Leu (FXIIIVal34Leu) polymorphism is associated with protection against myocardial infarction (MI) in Caucasians, in the absence of features of insulin resistance. The role of this polymorphism in the UK Asian population, with its high prevalence of insulin resistance and ischaemic heart disease, is unknown. We investigated the frequency of genotypes at this polymorphism, and measures of circulating FXIII in a group of UK Asians attending for coronary angiography. Genotype at the FXIIIVal34Leu polymorphism was not associated with MI. FXIII B-subunit levels correlated with waist: hip ratio (r = 0.19, p 0.005), HbA1c (r = 0.18, p 0.05), fasting triglycerides (r = 0.21, p 0.005), total cholesterol (r = 0.29, p 0.0005) and PAI-1 antigen (r = 0.24, p 0.005). An association between FXIIIVal34Leu and FXIII cross-linking activity was confirmed in these subjects (one-way ANOVA p 0.0005). This evidence does not support the hypothesis that FXIIIVal34Leu is protective against MI in the UK Asian population. FXIII B-subunit levels are strongly linked to risk factors for cardiovascular disease, suggesting an underlying association with insulin resistance.

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Identification of Potential Novel Interacting Partners for Coagulation Factor XIII B (FXIII-B) Subunit, a Protein Associated with a Rare Bleeding Disorder

International Journal of Molecular Sciences ◽

10.3390/ijms20112682 ◽

2019 ◽

Vol 20 (11) ◽

pp. 2682 ◽

Cited By ~ 3

Author(s):

Sneha Singh ◽

Mohammad Suhail Akhter ◽

Johannes Dodt ◽

Peter Volkers ◽

Andreas Reuter ◽

...

Keyword(s):

Factor Xiii ◽

Regulatory Protein ◽

Coagulation Factor ◽

Factor H ◽

Complement C3 ◽

Complement Factor ◽

B Subunit ◽

Coagulation Factor Xiii ◽

A Subunit ◽

Complement C1q

Coagulation factor XIII (FXIII) is a plasma-circulating heterotetrameric pro-transglutaminase complex that is composed of two catalytic FXIII-A and two protective/regulatory FXIII-B subunits. FXIII acts by forming covalent cross-links within a preformed fibrin clots to prevent its premature fibrinolysis. The FXIII-A subunit is known to have pleiotropic roles outside coagulation, but the FXIII-B subunit is a relatively unexplored entity, both structurally as well as functionally. Its discovered roles so far are limited to that of the carrier/regulatory protein of its partner FXIII-A subunit. In the present study, we have explored the co-presence of protein excipients in commercial FXIII plasma concentrate FibrogamminP by combination of protein purification and mass spectrometry-based verification. Complement factor H was one of the co-excipients observed in this analysis. This was followed by performing pull down assays from plasma in order to detect the putative novel interacting partners for the FXIII-B subunit. Complement system proteins, like complement C3 and complement C1q, were amongst the proteins that were pulled down. The only protein that was observed in both experimental set ups was alpha-2-macroglobulin, which might therefore be a putative interacting partner of the FXIII/FXIII-B subunit. Future functional investigations will be needed to understand the physiological significance of this association.

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