Factor XIII Val34Leu polymorphism modulates the prothrombotic and inflammatory state associated with atrial fibrillation.
Atrial fibrillation (AF) has been shown to confer a prothrombotic or hypercoagulable state, which could be related to inflammation. Factor XIII (FXIII) catalyses the cross-linking of fibrin monomers, increasing clot resistance; specifically, a common polymorphism, Val34Leu, in the FXIII-A subunit gene has been associated with more rapid FXIII activation. We hypothesised a role for this polymorphism in the prothrombotic state and inflammation in AF, and tested this hypothesis by measurement of indices of coagulation (tissue factor (TF) and fibrinogen), inflammation (interleukin-6 (IL6)) and platelet activation (soluble P selectin (sPsel)).


METHODS
We studied 90 stable outpatients (73 +/- 8 years) with persistent AF. The FXIII Val34Leu polymorphism was determined by polymerase chain reaction-allelic specific restriction assay (PCR-ASRA). Prevalence of Val34Leu polymorphism of patients was compared to 585 unrelated subjects from the same geographical area. Plasma fibrinogen (Clauss), TF, IL6 and sPsel (all ELISA) were quantified in patient group. Research indices were compared to 74 controls in sinus rhythm with similar clinical characteristics.


RESULTS
There were no statistical differences in FXIII polymorphism prevalence between AF patients and controls. Patients carrying the Leu34 allele had higher plasma levels of TF, IL6 and sPsel (all P < 0.05) compared to controls. Plasma IL6 and TF levels were significantly correlated (Spearman coefficient, r = 0.33, P < 0.01). On multivariate analysis, the Leu34 allele was independently associated with IL6 levels (P < 0.01), whereas TF levels were only associated with IL6 concentrations. However, sPsel and fibrinogen levels were not related to Leu34 allele.


CONCLUSIONS
FXIII Val34Leu polymorphism was independently associated with IL6 levels in AF. The Leu34 allele may potentially influence the prothrombotic state in these patients by modulating the inflammatory state.
Marín
Francisco
F
Cardiology Service, Hospital General Universitario, C/Pintor Baeza s/n, 03010 Alicante, Spain.
Corral
Javier
J
Roldán
Vanessa
V
González-Conejero
Rocío
R
del Rey
María Luz
ML
Sogorb
Francisco
F
Lip
Gregory Y H
GY
Vicente
Vicente
V
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics*; D001281:Atrial Fibrillation / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005176:Factor XIII / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D019007:P-Selectin / Q000097:blood; D011110:Polymorphism, Genetic; D013925:Thromboplastin / Q000032:analysis
D015850:Interleukin-6; D019007:P-Selectin; D005340:Fibrinogen; D005176:Factor XIII; D013925:Thromboplastin