Factor XIII-A subunit Val34Leu polymorphism is associated with the risk of thrombosis in patients with antiphospholipid antibodies and high fibrinogen levels

Abstract

SummaryRecent 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.

Prognostic analysis of 23 cases of undifferentiated thyroid carcinoma

“…It is synthesized and secreted by hepatocytes and consists of two pairs of α, β and γ chains.There are small peptides called fibrin A and fibrin B at the n-terminus of α and β peptide chains respectively, and fibrin A and B are specifically excised by thrombin to form polymeric reticulated fibrin monomers [15].Fibrinogen is mainly involved in the coagulation process of the body. Meanwhile, under the action of thrombin, its degradation products can provide stable adhesion and metastasis scaffold for tumor cells, so that tumor cells are easy to grow, metastasize and invade blood vessels to form tumor thrombi or tumor nuclear matrix [16][17]. Meanwhile, it not only promotes the formation of secondary tumors,Moreover, it also helps tumor cells escape the killing of therapeutic drugs [18][19], which are associated with poor prognosis of various malignant tumors.Relevant studies have found that plasma fibrinogen level in cancer patients is significantly higher than that in benign disease patients, and the level of fibrinogen is significantly increased during tumor recurrence or metastasis [20].The plasma fibrinogen of hepatocellular carcinoma patients is higher than that of hepatitis B cirrhosis patients, and the original fibrinogen value also increases with the increase of TNM stage [21].Other literatures have reported that high fibrinogen level often predicts shorter survival and poorer prognosis in cancer patients [22][23].…”

Risk for Early Pregnancy Loss by Factor XIII Val34Leu: The Impact of Fibrinogen Concentration

“…Controversial results have been published regarding the effect of the FXIII Val34Leu polymorphism on the development of CAD, peripheral artery disease, ischemic stroke, and venous thromboembolism .…”

“…In studies of the 34Leu where the impact of fibrinogen levels was taken into consideration, a protective effect of the 34Leu genotype was noted at fibrinogen levels in the upper normal range . Moreover, Boekholdt et al have demonstrated an elevated risk for developing disease at fibrinogen levels in the lower normal range .…”

Genetics of Antiphospholipid Syndrome

“…Nevertheless, the results showed that the F13A1 Leu 34 allele had no protective effect in the development of thrombosis in patients with APS. On the contrary, De la Red et al found that this polymorphism was associated with a higher risk of thrombosis in patients with the presence of both aPL antibodies and high fibrinogen levels (de la Red et al, 2009). They found no significant differences in F13A1 Leu 34 allele frequencies between primary APS, APS/SLE, SLE-aPL and asymptomatic-aPL patients, or between patients with and without thrombosis.…”