[ protective effect of FXIII Val34Leu polymorphism against deep vein thrombosis: a report from Iranian Blood Transfusion Organization [IBTO]]

The coagulation factor XIII is a pro-transglutaminase enzyme with tetrameric structure. An exchange of G for A in exon 2 of A subunit results in replacement of valine with leucine in amino acid 34. As a result of this substitution mutation, the clots produced are fragile and loose therefore it seems that FXIII Val34Leu polymorphism acts as a factor for individual protection against thrombosis Objectives: To determine the prevalence and role of FXIIIA Val34Leu polymorphism against deep vein thrombosis. This was a retrospective case-control study performed on 116 patients with DVT who were referred to Thrombosis and Homeostasis Laboratory affiliated to Iranian Blood Transfusion Organization. Also, 100 healthy individuals [blood donors] were recruited as control. Following DNA extraction and application of PCR and RFLP techniques in presence of restriction enzyme Cfo1, the genotypes of FXIII Val34Leu polymorphism were identified. The data were analyzed using chi square test as well as calculation of OD ratio and 95% confidence interval. The prevalence of FXIII Val34Leu polymorphism among the case and control groups was 22.4% and 37.4%, respectively. While the allele frequency of leucine in case group was 14.7% it was 20.2% in control group. No significant correlation between polymorphism and sex was established. According to our data, no association between the FXIII Val34Leu polymorphism and protection against deep vein thrombosis was demonstrated. Therefore, it seems that this polymorphism occurs as a natural phenomenon and unaffected by gender

Effects of Val34Leu and Val35Leu polymorphism on the enzyme activity of the coagulation factor XIII-A

Change in fibrin stabilizing activity of factor XIII A subunit (FXIII-A) caused by a specific mutation, Val34Leu, is recently implicated to incidences of pathophysiology of thrombosis. In an effort to understand the effect of Val34Leu on enhanced catalytic role of FXIII-A, wild type human factor XIII A (HFXIII-A) and mutant HFXIII-A: HFXIII-A (V34L), HFXIII-A (V35L) and HFXIII-A (V34L/V35L) cDNA were expressed in E.coli system where the purified recombinant FXIII-A (rFXIII-A) showed a similar specific transglutaminase activity comparable to the human native FXIII-A from platelet. Using these rFXIII-A mutants, the activation kinetics by thrombin and the enzymatic properties of the activated rFXIII-A were characterized. rFXIII-A (V34L) and rFXIII-A (V34L/V35L) mutants were activated by thrombin much faster than those of wild type rFXIII-A and V35L variant. However, the activated rFXIII-A and mutants showed the identical catalytic efficiency as measured by in vitro assay. These results suggest that ready activation caused by a specific mutation of neighboring thrombin cleavage site(s) in the activation peptide of FXIII-A like V34L resulted in the real-time amount of the activated factor XIII-A that could influence the outcome of fibrin stabilization in vivo such as alpha2- plasmin inhibitor crosslinking to fibrin, a reaction known to be dependent on the initial concentration of active factor-XIII-A.

No Association of Factor XIII Val34Leu Polymorphism with Primary Intracerebral Hemorrhage and Healthy Controls in Korean Population

The polymorphism in the factor XIII A-subunit gene (FXIII Val34Leu) has been recognized as a risk factor for primary intracerebral hemorrhage (PICH). In addition, FXIII Val34Leu has a significant ethnic heterogeneity. FXIII Val34Leu was detected in 41.7-54.8% of the Westerners, but in 2.5% of the Asians. We aimed to evaluate the prevalence of FXIII Val34Leu in patients with PICH and in healthy controls among Koreans. We recruited 58 in-patients with PICH, defined by brain computed tomography or magnetic resonance imaging, and 48 controls matched for age, sex, and risk factors for cerebrovascular diseases. Genomic DNA was extracted from blood. A 183-bp fragment of exon 2/intron B of the factor XIII Asubunit gene was amplified by polymerase chain reaction (PCR). The factor XIII genotype was determined through a single-stranded conformational polymorphism. Fifty-eight patients and 48 controls showed the same band patterns on SSCP. In addition, we directly sequenced six random-selected DNA segments using DNA auto-sequencer. In conclusion, the results of this study suggest that FXIII Val34Leu be absent or rare both in patients with PICH and in healthy controls among Koreans.