Factor XIII Val34Leu Research Articles

Cancer-associated thrombosis: the role of inherited thrombophilia.

Cancer-associated thrombosis (CAT) is a common complication and a major cause of morbidity and mortality in patients with active cancers. CAT is common in various malignancies, particularly pancreatic, ovarian, gastric, colorectal, and hematologic cancers. In fact, CAT is a complicated multifactorial complication that may be influenced by the type of cancer as well as by the genetic background and inheritance of thrombophilic variants and elevated concentrations of coagulation factors. Several studies have shown the prominent role of inherited thrombophilias, such as prothrombin 20210, factor V Leiden, factor XIII Val34Leu, MTHFR C677T, in the occurrence of CAT, while others have found no correlation between them and CAT. In the present review, we have attempted to investigate the possible role of inherited thrombophilia in the occurrence of CAT.

Comprehensive evaluation of genetic and acquired thrombophilia markers for an individualized prediction of clinical thrombosis in patients with lymphoma and multiple myeloma

Patients diagnosed with lymphoma or multiple myeloma are at elevated risk of venous thromboembolism (VTE). Optimum risk stratification and effective thromboprophylaxis can only be achieved through the development of a multiple-specific risk score that successfully captures all aspects of the heterogeneous prothrombotic environment existing in these patients. Our aim was to identify risk factors for thrombosis and suggest an improved tool combining clinical data, thrombo-inflammatory biomarkers and genetic (Thrombo inCode® test) variables for predicting thrombotic risk in patients with lymphoma and multiple myeloma. A prospective longitudinal study was conducted on newly-diagnosed lymphoma and multiple myeloma patients who presented at our institution between February 2020 and January 2021. The study included 47 patients with lymphoma and 16 patients with multiple myeloma. We performed a follow-up of 1 year or until September 2021. The incidence of venous thrombosis and associated risk factors were analysed, including the genetic Thrombo inCode® test. Khorana and ThroLy scores for lymphoma patients and IMPEDE VTE score for myeloma patients were calculated. At a median follow-up of 9.1 months, VTE incidence was 9.5% (6/63), with 4 and 2 patients with lymphoma and myeloma who developed the events, respectively. Univariate analysis showed that the incidence of thrombosis was significantly higher in patients with ECOG ≥ 2 and prior immobility. Median factor VIII levels were significantly higher in patients with thrombosis (with increased values in all of them). Moreover, there was a trend in genetic variant rs5985 (factor XIII) as a protective factor, and a trend to higher thrombotic risk in patients with factor V Leiden, rs2232698 variant (serpinA10), low total protein S activity, elevated D-dimer, aggressive lymphoma and treatment with dexamethasone. The results of our study demonstrate promise for the potential use of widely accessible markers to increase precision in risk prediction for VTE in patients with lymphoma and multiple myeloma, particularly ECOG ≥ 2, immobility and higher factor VIII levels, as well as lymphoma aggressiveness, treatment with dexamethasone and the haemostatic biomarkers D-dimer and total protein S activity. Additionally, genetic variants factor V Leiden, serpinA10 rs2232698 and factor XIII-A Val34Leu warrant further investigation for use in the research setting.Graphical

Detection of human platelets antigen polymorphism (HPA-1 and HPA-3) and human factor XIII mutation in Sudanese women with recurrent pregnancy loss

BackgroundRecurrent pregnancy Loss (RPL) is common problem affecting many couples. A certain genetic variants link to increase the danger of this condition particularly HPA-1, HPA-3 and Human Factor XIII Val34Leu Mutation. The present study aims to find an association between RPL and the Factor XIII Val34Leu polymorphism, as well as HPA-1 and HPA-3 in Sudanese women with RPL.MethodsThis case-control study conducted between June 2022 and December 2022 included 216 women, with 103 cases having minimum three abortions in the past, and 113 healthy controls with at least two full-term births and no abortion history. DNA was isolated from whole blood and the status of three genetic polymorphisms (HPA-1, HPA-3, and factor XIII) was done using a polymerase chain reaction (PCR). Data was analysed using the SPSS version 24 software.ResultsThe A/A genotype was found to be more prevalent in cases (79.6%) and controls (96.5%) regarding HPA-1. A significant difference was observed in overall allele frequency for B allele (97.0%) and expected frequency of A allele was (81.1%) using the Hardy-Weinberg distribution (p < 0.001). The genotype A/A was most common in these patients (90.3%) and controls (100%), while B/B genotype was only (9.7%) in patients regarding HPA-3. Furthermore, the frequency of Val/Val genotype was higher in cases (88.3%) as compared with controls (90.3%). The risk of RPL in patients was nearly the same in Val/Leu individuals and controls group but all these differences were not statistically significant (p > 0.05).ConclusionOur results indicate a link between Human Platelet Antigen-1 (HPA-1), Human Platelet Antigen-3 (HPA-3) and Factor XIII gene polymorphism with RPL.

Markers of Hereditary Thrombophilia with Unclear Significance.

Thrombophilia leads to an increased risk of venous thromboembolism. Widely accepted risk factors for thrombophilia comprise deficiencies of protein C, protein S, and antithrombin, as well as the factor V "Leiden" mutation, the prothrombin G20210A mutation, dysfibrinogenemia, and, albeit less conclusive, increased levels of factor VIII. Besides these established markers of thrombophilia, risk factors of unclear significance have been described in the literature. These inherited risk factors include deficiencies or loss-of-activity of the activity of ADAMTS13, heparin cofactor II, plasminogen, tissue factor pathway inhibitor (TFPI), thrombomodulin, protein Z (PZ), as well as PZ-dependent protease inhibitor. On the other hand, thrombophilia has been linked to the gain-of-activity, or elevated levels, of α2-antiplasmin, angiotensin-converting enzyme, coagulation factors IX (FIX) and XI (FXI), fibrinogen, homocysteine, lipoprotein(a), plasminogen activator inhibitor-1 (PAI-1), and thrombin-activatable fibrinolysis inhibitor (TAFI). With respect to the molecular interactions that may influence the thrombotic risk, more complex mechanisms have been described for endothelial protein C receptor (EPCR) and factor XIII (FXIII) Val34Leu. With focus on the risk for venous thrombosis, the present review aims to give an overview on the current knowledge on the significance of the aforementioned markers for thrombophilia screening. According to the current knowledge, there appears to be weak evidence for a potential impact of EPCR, FIX, FXI, FXIII Val34Leu, fibrinogen, homocysteine, PAI-1, PZ, TAFI, and TFPI on the thrombotic risk.

Association of factor V Leiden R506Q, FXIIIVal34Leu, and MTHFR C677T polymorphisms with acute myocardial infarction

BackgroundAcute myocardial infarction (AMI) is a leading cause of death and morbidity around the world. Although the association between thrombophilia and AMI is well-established, controversial data are present on the association between thrombophilic polymorphisms and AMI. The aim of this study was to investigate the association of three thrombophilic polymorphisms including factor V Leiden (FVL), MTHFRC677T (methylenetetrahydrofolate reductase), and Coagulation factor XIIIVal34Leu with AMI in East of Iran.ResultThere were no statistically significant differences between the patients and control groups in terms of the distributions of allelic and genotypic frequencies of FVL and FXIIIVal34Leu polymorphisms (P-value > 0.05). Subjects who carried CT genotype of MTHFR C677T polymorphism were at a 2.03-fold higher risk for AMI (P-value: 0.02, OR 1.76, 95% CI 1.07–2.75). Furthermore, patients with MTHFR 677CT (P-value < 0.001, β = - 0.90, 95% CI − 1.33, − 047) or 677CC (P-value < 0.001, β = - 1.04, 95% CI − 1.47, − 0.61) genotypes showed significantly Lower creatinine levels compared with patients having the MTHFR 677TT. No association was observed between the other remaining polymorphisms and AMI (P-value > 0.05).ConclusionOur findings showed that MTHFRC677T polymorphism could contribute to AMI susceptibility and increase creatinine levels in east Iran population. This was the first study to examine the association of these three polymorphisms with AMI in east Iran.

Coagulation Factor XIII Val34Leu Polymorphism in the Prediction of Premature Cardiovascular Events-The Results of Two Meta-Analyses.

Background: Polymorphisms within the gene that encodes for coagulation factor XIII (FXIII) have been suggested to be involved in the pathogeneses of ischemic stroke (IS) and myocardial infarction (MI). The Val34Leu polymorphism is one of the most commonly analysed FXIII polymorphisms. However, studies on the role of the Val34Leu polymorphism in the aetiology of vascular diseases often show contradictory results. In the present meta-analysis, we aimed to pool data from available articles to assess the relationship between the FXIII Val34Leu polymorphism and the susceptibilities to IS of undetermined source and premature MI in patients aged below 55 years. Methods: We searched databases (PubMed, Embase, Google Scholar, SciELO, and Medline) using specific keywords (the last search was in January 2022). Eventually, 18 studies (627 cases and 1639 controls for IS; 2595 cases and 4255 controls for MI) met the inclusion criteria. Data were analysed using RevMan 5.4 and StatsDirect 3 link software. The relation between Val34Leu polymorphism and disease was analysed in five genetic models, i.e., dominant, recessive, additive, heterozygous, and allelic. Results: No relation between Val34Leu polymorphism and IS in young adults was observed in all analysed genetic models. For premature MI, significant pooled OR was found between the carrier state of the Leu allele (Val/Leu + Leu/Leu vs. Val/Val) and a lack of MI, suggesting its protective role (OR = 0.80 95%CI 0.64–0.99, p = 0.04). A similar finding was observed for the heterozygous model in MI (Val/Leu vs. Val/Val) (OR = 0.77 95%CI 0.61–0.98, p = 0.03). No relation was found for the recessive, additive, and allelic models in MI. Conclusions: In the population of young adults, no positive correlation was found between the FXIII Val34Leu polymorphism and IS of undetermined source in any of the analysed genetic models. In turn, the carrier state of the 34Leu allele as well as FXIII heterozygotes themselves were found to play a protective role in relation to premature MI.

Factor XIII-A Val34Leu and Tyr204Phe variants influence clot kinetics in a cohort of South African type 2 diabetes mellitus patients

Factor XIII, a transglutaminase that plays a crucial role in clot formation, consists of subunits A and B. Single nucleotide polymorphisms in Factor XIII-A have been linked to thrombotic risk. In Type 2 Diabetes mellitus (T2DM), a hypercoagulable state is thought to contribute to the high mortality rate associated with thrombotic diseases. Due to the lack of prevalence data of FXIII-A single nucleotide polymorphisms (SNPs) in T2DM in a South African cohort, this study assessed the prevalence FXIII-A Val34Leu (rs5985) and Tyr204Phe (rs3024477) SNP’s and the effect on clot kinetics in T2DM. Materials and methodsA cohort of T2DM patients (n = 100) and race, age and gender matched healthy controls (n = 101) were recruited following ethical approval. Thromboelastography® (TEG®) was used to assess the viscoelastic properties in platelet poor plasma (PPP) in controls (n = 91) and T2DM patients (n = 91) younger than 50 years old. Genomic DNA was isolated from whole blood using the Quick-DNA™ Miniprep Plus Kit and PCR-RFLP was used to genotype each sample for FXIII-A rs5985 and rs3024477 SNPs. ResultsTEG® analyses indicated a longer R-time (p < 0.0001) and higher TMRTG (p < 0.0001) in PPP of T2DM patients. Control and T2DM genotype distribution conformed to Hardy-Weinberg equilibrium (p > 0.05). There was a higher prevalence of the wildtype genotype of FXIII-A Tyr204Phe (rs3024477) SNP in T2DM (OR = 0.23, 95% CI = 0.12–0.42, p < 0.0001). The 204Phe variant was more frequent in the Caucasians (OR = 0.39, 95% CI = 0.05–0.33, p < 0.0001). The presence of the 204Phe variant in T2DM affected TMRTG (p = 0.0207). The variant affected R time (p = 0.0432) and TMRTG (p = 0.0209 and p = 0.0207) in controls and T2DM, respectively. ConclusionAn inverse association with T2DM and FXIII-A Tyr204Phe was found. A hypo coagulable PPP clot profile was observed in T2DM. A shorter reaction time was observed and but faster rate at which the clot reached maximum strength in both controls and T2DM in the presence of the 204Phe variant.

Decreased clot burden is associated with factor XIII Val34Leu polymorphism and better functional outcomes in acute ischemic stroke patients treated with intravenous thrombolysis

Intravenous thrombolysis using recombinant tissue plasminogen activator remains the mainstay treatment of acute ischemic stroke (AIS), although endovascular treatment is becoming standard of care in case of large vessel occlusions (LVO). To quantify the thrombus burden in LVO, a semiquantitative CT angiography (CTA) grading system, the clot burden score (CBS) can be used. Here we aimed to study the association between CBS and various hemostasis parameters, and to evaluate which parameters are major determinants of thrombolysis outcome. In this single-centered prospective observational case-control study, 200 anterior circulation AIS patients receiving intravenous thrombolysis treatment without thrombectomy were enrolled: 100 AIS patients with LVO (CBS 0-9) and 100 age- and sex-matched AIS patients without LVO (CBS 10). Fibrinogen, α2-plasmin inhibitor, plasminogen, factor XIII and D-dimer were assessed from blood samples taken before and 24 h after thrombolysis, and FXIII-A Val34Leu was genotyped. CBS was calculated using admission CTA. Short-term outcomes were defined based on the change in NIHSS by day 7, long-term outcomes were assessed according to the modified Rankin scale at 3 months post-event. Poor outcomes were significantly more frequent in the CBS 0-9 group. Plasminogen activity on admission was significantly higher in the CBS 0-9 group. In a univariate analysis, significant protective effect of the Leu34 allele against developing larger clots (CBS 0-9) could be demonstrated (OR:0.519; 95%CI:0.298-0.922, p = 0.0227). Multivariate regression analysis revealed that CBS is an independent predictor of short- and long-term functional outcomes, while such effect of the studied hemostasis parameters could not be demonstrated. CBS was found to be a significant independent predictor of thrombolysis outcomes. FXIII-A Leu34 carrier status was associated with smaller thrombus burden, which is consistent with the in vitro described whole blood clot mass reducing effects of the allele, but the polymorphism had no effect on thrombolysis outcomes.

Combinations of fibrinolytic gene polymorphisms (plasminogen activator inhibitor type 1 4G/5G, factor XIII Val34Leu and angiotensin-converting enzyme I/D) in women with idiopathic infertility.

During normal pregnancy depressed fibrinolytic system is caused by changes in many factors, which could be influenced by different gene polymorphisms. The aim of this study was to investigate the combination of fibrinolysis-related gene polymorphisms in women with idiopathic infertility. We genotype polymorphisms 4G/5G in plasminogen activator inhibitor type 1 (PAI-1), Val34Leu in factor XIII (FXIII) and I/D in angiotensin-converting enzyme (ACE) gene. The patients group consisted of 83 females with idiopathic infertility, while the control group included 121 females with at least one born child. The alleles and genotypes distributions showed no significant differences between analyzed groups. Although higher frequency of PAI-1 5G5G genotype in patients did not reach statistical significance, 5G5G genotype of PAI-1 in combination with ValVal genotype of FXIII leads to higher risk for infertility (P < 0.05). In addition, when we added ACE I/D polymorphism in analysis, the 4G in PAI-1 and D allele in ACE, showed protective effect in combination with FXIII polymorphism (P < 0.05). The finding that combined homozygosity of 5G of PAI-1, commonly associated with greater fibrinolytic activity and bleeding tendency, in combination with Val genotype of FXIII impose a risk for female idiopathic infertility. The protective effect of alleles 4G (PAI-1) and D (ACE) suggest that different combinations of polymorphisms influencing fibrinolysis could lead to better established hemostatic balance and reproductive success. Further analyses, with larger number of samples, as well as assessment of additional biochemical parameters of fibrinolysis, should be performed to clarify the role of gene polymorphisms on fibrinolysis and consequently their influence on reproductive success.

The Angiotensin-converting Enzyme Insertion/Deletion Polymorphism as a Common Risk Factor for Major Pregnancy Complications.

Idiopathic pregnancy complications pose a major threat to both maternal and fetal health worldwide. Numerous studies have implicated the role of the renin-angiotensin system (RAS) in the development of obstetric syndromes, since it is crucial for the uteroplacental function. A major RAS component is the angiotensin-converting enzyme (ACE), which hydrolyses angiotensin I to angiotensin II, and not only regulates arterial pressure, but also fibrinolytic activity, indirectly, through the expression of plasminogen activator inhibitor-1. A key functional polymorphism of the ACE gene is the insertion/deletion (I/D) polymorphism, which affects gene expression and product levels, and can therefore lead to high blood pressure and/or reduced fibrinolytic activity. These can cause major pregnancy complications, such as preeclampsia, recurrent pregnancy loss and preterm birth. This review discusses how the ACE I/D is associated with susceptibility towards pregnancy complications, on its own or in combination with other functional gene polymorphisms such, as the angiotensin II receptor type 1 (AT1R) A1166CC, angiotensin II receptor type 2 (AT2R) G1332A, plasminogen activator inhibitor-1 (PAI-1) 4G/5G, matrix metallopeptidase-9 (MMP-9) C1562T, angiotensinogen (AGT) M235T, renin (REN) 83A/G, factor XIII (F13) Val34Leu and endothelial nitric oxide synthase (eNOS) 4a/b.

The role of thrombophilia genes in the clinical implementation of arterial and venous thrombosis in newborns

The article considers the analysis results of the occurrence frequency of genotypes and alleles of plasma, platelet and fibrinolytic hemostasis in full-term newborns with arterial and venous thrombosis of various localization. Gene polymorphisms were studied by real-time PCR in human DNA samples obtained from buccal epithelium and venous blood lymphocytes. The control group was a group of healthy full-term newborns from families without a thrombophilic history. Predictors of arterial and venous thrombosis in children are such as polymorphism of the plasminogen activator inhibitor gene PAI-1-675 4G/4G (OR=5,6 [2,3-13,8]), combinations of polymorphisms PAI-1-675 4G/4G + factor VII G10976A G/G (OR=5,8 [1,7-19,1]), combinations of polymorphisms PAI-1 -675 4G/4G + factor VII G10976A G/G + factor XIII Val34Leu G/G (% AR=61), fibrinogen FGB -455 G/A (OR=3,75 [1,4-9,4]) and integrin alpha 2 ITGA2 807 T/T (OR=15,56 [1,9-126,7]). Thus, the study of polymorphisms of the plasminogen activator inhibitor, fibrinogen, integrin alpha 2 can serve as one of the criteria for identifying a high-risk group for the development of arterial and venous thrombosis in newborns and should be taken into account when evaluating individual thrombophilia risk.

Faster fibrin clot degradation characterizes patients with central pulmonary embolism at a low risk of recurrent peripheral embolism

It is unclear whether thrombus location in pulmonary arteries is associated with particular clot characteristics. We assessed 156 patients following either central or peripheral pulmonary embolism (PE). Plasma clot lysis time, the rate of D-dimer release from plasma clots (D-Drate) with the maximum D-dimer concentration achieved (D-Dmax), as well as fibrin formation on turbidimetry, plasma clot permeation, thrombin generation, and fibrinolytic parameters were measured 3–6 months after PE. Patients following central PE (n = 108, 69.3%) were more likely smokers (38.9% vs 18.8%; p = 0.01), less likely carriers of factor XIII Val34Leu allele (40.7% vs 62.5%, p = 0.01), exhibited 16.7% higher D-Drate and 12.7% higher tissue plasminogen activator antigen (tPA:Ag) compared with peripheral PE (p = 0.02 and p < 0.0001, respectively). Saddle PE patients (n = 31, 19.9%) had 11.1% higher D-Drate and 7.3% higher D-Dmax compared with central PE (both p < 0.05). Twenty-three recurrent PE episodes, including 15 central episodes, during a median follow-up of 52.5 months were recorded. Plasma D-dimer and tPA:Ag were independent predictors for central recurrent PE, whereas D-Drate and peak thrombin predicted peripheral recurrent PE. Plasma clots degradation is faster in patients following central PE compared with peripheral PE and fibrinolysis markers might help to predict a type of recurrent PE.

Polymorphisms of Plasminogen Activator Inhibitor-1 4G/5G, Coagulation Factor XIII Val34Leu and Angiotensin Converting Enzyme I/D Impact on Recurrent Implantation Failure

Polymorphisms of Plasminogen Activator Inhibitor-1 4G/5G, Coagulation Factor XIII Val34Leu and Angiotensin Converting Enzyme I/D Impact on Recurrent Implantation Failure

Association of genetic variants of hemostatic genes with myocardial infarction in Egyptian patients

Hemostatic genes polymorphisms are well known to be associated with venous thrombosis, but their association with arterial thrombosis especially myocardial infarction (MI) remains to be clarified. We investigated the role of three hemostatic gene polymorphisms, prothrombin G20210A, factor XIII (FXIII) Val34Leu (G/T), and fibrinogen-β-455G/A and their coexistence in Egyptian patients with MI. The possible correlation of these polymorphisms with plasma fibrinogen level was also evaluated. The study included 120 patients with MI and 60 healthy volunteers. Gene polymorphisms were tested using multiplex polymerase chain reaction and reverse-hybridization technique. Plasma fibrinogen level was determined by ELISA. Our study showed an increased risk of MI with fibrinogen β-455G/A heterozygosity as well as FXIII Val34Leu homo and heterozygosity. In addition, the FXIII T allele (Leu34) and fibrinogen β-455A allele were significantly associated with MI. Conversely, the prevalence of prothrombin mutation did not differ between patients with MI and controls. Combined carriers of FXIII Leu34 and fibrinogen-β455A alleles were at higher risk of MI, whereas combined FXIII Val34Leu and prothrombin 20210A polymorphisms did not show increased risk for MI compared with controls. Plasma fibrinogen levels were significantly higher in patients with MI than controls. In MI patients, plasma fibrinogen levels were significantly higher in those with FXIII GT/TT or fibrinogen β-455 GA, while were significantly lower in those with prothrombin 20210 GA compared with patients with wild type genotypes. In conclusion, our results suggest a possible thrombotic predisposition of FXIII Val34Leu, fibrinogen β-455G/A polymorphisms and their coexistence for MI. These polymorphisms may add complexity to disease pathology by increasing plasma fibrinogen level. Extended studies are needed to confirm our results; nevertheless, these data may be implicated in genetic counseling and screening of high-risk individuals.

Effects of coagulation factor XIII (Val34Leu) polymorphism on recurrent pregnancy loss in Iranian Azeri women

Abstract Background: Recurrent pregnancy loss (RPL) is a heterogeneous condition consisting of two or more consecutive abortions occurring before 20 weeks of gestation. One of the clotting factor genes encodes factor XIII (FXIII), which is involved in fibrin formation. The most common polymorphism in the FXIII genes is the conversion of G to T in exon 2 (val34leu) of the FXIIIA gene, which leads to the substitution of valine with leucine. The objective of this study was to investigate the association between RPL and FXIII val34leu polymorphisms in a sample population of Iranian Azeri women. Methods: A prospective case-control study was performed on a cohort of 310 RPL patients and 290 healthy controls. DNA was extracted from the whole blood and fragments of the Val34Leu polymorphism were amplified by polymerase chain reaction (PCR), followed by DNA sequencing. Genotyping was performed using the Sequenom MassArray system. Results: The genotype frequencies of FXIII in the case group were 60.64% GG, 34.83% GT, and 4.41% TT, whereas the frequencies in the control group were 58.96% GG, 36.5% GT, and 4.48% TT. T allele frequencies in the case and control groups were 78.06% and 21.93%, respectively, and G allele frequencies were 77.24% and 22.75%, respectively. Conclusions: No significant association was observed between the Val34Leu polymorphism and RPL among Iranian Azeri women.

Association of factor XIII Val34Leu polymorphism and coronary artery disease: A meta-analysis.

Factor XIII plays an important role in the stabilization of the linkage between fibrins and in the pathophysiology of coronary artery disease (CAD). The association between factor XIII Val34Leu polymorphism and CAD risk remains controversial. We conducted a meta-analysis of 36 studies involving 26,940 cases and 34,694 controls. Subgroup analyses were performed with division of data into disease (myocardial infarction [MI], CAD without MI), age, and sex. Factor XIII Val34Leu polymorphism was significantly associated with ove all CAD risk (odds ratio [OR] = 1.09, 95% confidence interval [CI] = 1.03-1.06, p = 0.004) and MI risk (OR = 1.15, 95% CI 1.07-1.25, p = 0.0003), but not with CAD without MI risk (OR = 1.00, 95% CI 0.87-1.15, p = 0.96). In the subgroup analysis by age and sex, there was no association between Val34Leu polymorphism and CAD. This meta-analysis found that factor XIII Val34Leu polymorphism was associated with CAD risk, especially MI, but not with CAD without MI. In addition, age and sex did not affect the relationship between factor XIII Val34Leu polymorphism and CAD risk.

Factor XIII Val34Leu polymorphism and risk of recurrent pregnancy loss in Iranian population: a case control study

Recurrent pregnancy loss (RPL) is a heterogeneous condition and thrombophilias have been considered as a probable cause. The aim of this study was to investigate the prevalence of the coagulation factor XIII Val34Leu polymorphism among women with unexplained RPL. A total of 140 women with a history of unexplained RPL and 100 age-matched healthy fertile women were recruited. The presence of FXIII Val34Leu polymorphism among the cases and controls was investigated using PCR-RFLP method. Genotype analyses of the subjects revealed that the patients had a significantly higher prevalence of V/L and L/L than the controls (P<0.05): 33.5% vs. 15%, and 9.2% vs. 2%, respectively. These results indicate a significant association between FXIII Val34Leu polymorphism and unexplained RPL in the Iranian patient.

Association of Hemostatic Gene Polymorphisms With Early-Onset Ischemic Heart Disease in Egyptian Patients.

The association between hereditary thrombophilia and venous thrombosis is well established but controversial data exist with respect to arterial thrombosis. We performed a pilot study on 31 patients with acute myocardial infarction (AMI), 21 patients with unstable angina (UA), and 20 healthy volunteers to investigate the role of various hemostatic gene polymorphisms in young Egyptian patients, who survived their first ischemic heart disease (IHD). Thrombophilic gene polymorphisms were tested using multiplex polymerase chain reaction and reverse-hybridization technique. We showed an increased risk of AMI with factor V (FV) Leiden and prothrombin G20210A heterozygosity. The increased risks of UA was associated with GA and A allele of fibrinogen β-455G→A polymorphism. Conversely, factor XIII (FXIII) Val34Leu GT and T allele were protective in the UA group. Nevertheless, the prevalence of FV H1299R, plasminogen activator inhibitor 1 4G/5G, glycoprotein IIIa C1565T, 5,10-methylenetetrahydrofolate reductase C677T, and A1298C mutations did not differ between patients with IHD and controls. The data have clinical implications regarding screening and thromboprophylaxis in high-risk individuals younger than 40 years.

VAL34LEU POLYMORPHISM DETECTION BY REAL TIME PCR ASSAY USING

Factor XIII (FXIII) Val34Leu is the most important polymorphism of the A subunit in factor XIII gene. The aim of the present study was to develop an efficient method based on real time PCR with Fluorescence resonance energy transfer (FRET) detection and melting curve analysis for the detection of Val34Leu polymorphism. Specific primers were used to amplify the relevant fragment of the factor XIII-A gene and fluorescence resonance energy transfer hybridization probes were used for detection in a Rotor-Gene Q 5Plex HRM platform. Melting temperature (Tm) for the wild type was at 68.8, while Tm for homozygote mutant was at 63.8; heterozygote demonstrated both peaks. Our results showed that primers and probes propoesd in this study demonstrated a high specificity to identify wild type , heterozygous and homozygous mutantgenotypes. Due to the increasing molecular diagnosis in developing countries and the importance of identifying polymorphisms, this real time PCR assay is of great importance. An important advantage of this approach is the high sensitivity and specificity.

Prevalence of the Factor XIII Val34Leu Polymorphism in Korean Patients with Deep Vein Thrombosis

According to recent reports, a common polymorphism resulting in Val to Leu substitution, located 3 amino acids (Val34Leu) upstream of the thrombin cleavage site of FXIII A, has been related to a lower incidence of deep vein thrombosis (DVT). And, a different expression pattern has been shown across nations and races. However, the frequency of FXIII polymorphism expression in Koreans has not been reported in normal individuals or DVT-patient groups. Case-control study in Korean population. We investigated the distribution of factor XIII Val34Leu polymorphisms in Korean patients of DVT (50 cases) and Korean healthy controls (100 cases), using real-time polymerase chain reaction for single nucleotide polymorphism genotyping. With regard to the frequency of the FXIII polymorphism in DVT patients and in the general control group, all 50 cases in the patient group and 100 cases in the control group were found to be Val34 homozygotes. The Val34Leu polymorphism of FXIII was not found in Korean people, and compared with Caucasians, a noticeably low incidence of DVT was shown. Thus, the preventive effect of the Val34 allele of FXIII on the formation of thrombi was shown.