title: Factor XIII-A subunit Val34Leu polymorphism is associated with the risk of thrombosis in patients with antiphospholipid antibodies and high fibrinogen levels.
abstract: Recent reports have described the factor XIII A subunit (FXIII-A) Val34Leu polymorphism as a protective factor against venous and arterial thrombosis. The aim of this study was to investigate the association between the FXIII-A Val34Leu polymorphism, its interaction with fibrinogen concentration, and thrombosis in patients with antiphospholipid antibodies (aPL). We included 172 consecutive patients with aPL: 88 with primary antiphospholipid syndrome (APS), 38 with APS associated with systemic lupus erythematosus (APS-SLE), 32 with SLE and aPL but without APS (SLE-aPL), and 14 asymptomatic individuals with aPL (A-aPL). The FXIII-A Val34Leu polymorphism was assessed by polymerase chain reaction techniques. We found no significant differences in FXIII-A Leu34 allele frequencies between primary APS (allele frequency 0.22), APS-SLE (0.23), SLE-aPL (0.22) and A-aPL (0.32) patients, or between patients with (0.21) and without thrombosis (0.26). FXIII-A Leu34 allele frequencies were significantly lower in patients with thrombosis and those in the upper fibrinogen tertile (>3.40 g/l) (allele frequency 0.07) compared with patients without thrombosis in the upper fibrinogen tertile (0.29) and patients with (0.29) and without (0.25) thrombosis in the mid- and lower fibrinogen tertiles. The FXIII-A Leu34 allele had a protective effect against thrombosis in patients in the upper fibrinogen tertile (odds ratio [OR] = 0.20, 95% confidence interval [CI] 0.07-0.60) but not in those in the other tertiles (OR = 1.20, 95% CI 0.67-2.16). The FXIII-A Leu34 allele seems to have a protective effect on the development of thrombosis in patients with aPL, but only in those with high plasma fibrinogen values.
authors.affiliation: Department of Hemotherapy and Hemostasis, Hospital Clinic, Villarroel 170, 08036 Barcelona, Catalonia, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: de la Red
authors.forename: Dolores
authors.initials: D
authors.lastname: Tàssies
authors.forename: Gerard
authors.initials: G
authors.lastname: Espinosa
authors.forename: Joan
authors.initials: J
authors.lastname: Monteagudo
authors.forename: Albert
authors.initials: A
authors.lastname: Bové
authors.forename: Joan
authors.initials: J
authors.lastname: Plaza
authors.forename: Ricard
authors.initials: R
authors.lastname: Cervera
authors.forename: Joan-Carles
authors.initials: JC
authors.lastname: Reverter
mesh_terms: D000328:Adult; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000150:complications / Q000235:genetics*; D016022:Case-Control Studies; D005176:Factor XIII / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000032:analysis*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007930:Leucine; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D021122:Protein Subunits; D018570:Risk Assessment; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000235:genetics*; D015854:Up-Regulation; D014633:Valine
chemical_list: D021122:Protein Subunits; C064015:factor XIII subunit A; D005340:Fibrinogen; D005176:Factor XIII; D007930:Leucine; D014633:Valine