FXIII Val34Leu Polymorphism Research Articles

Factor V Leiden, MTHFR, and FXIIIVal34Leu gene polymorphisms and their association with clinical features and risk of diabetic retinopathy in patients with type 2 diabetes.

Diabetic retinopathy (DR) is expanding to epidemic levels globally due to the progressing prevalence of diabetes mellitus (DM). In this study, the association between factor V Leiden (FVL), MTHFRC677T, and FXIIIVal34Leu polymorphisms and diabetic retinopathy was investigated in Eastern Iran. This case-control study enlisted the participation of 300 people (diabetic patients=100, diabetic retinopathy patients=100, healthy controls=100), and polymorphisms were examined by Tetra primer ARMS-PCR. The frequency of FVL (p=0.294) and FXIIIVal34Leu (P=0.349) polymorphism showed no significant results between the genotype frequency in the mentioned groups. In contrast, MTHFRC677T SNP was significantly different in diabetic patients and controls (P=0.008). The MTHFRC677T polymorphism was foundtobeconnectedwithincreased systolic blood pressure in patients who had the TT genotype (130.96±11.92mm/Hg; P=0.011). Our study recommended that the MTHFRC677T polymorphism may offer to DR development. Studies with larger sample sizes and a wider spectrum of populations are authorized to verify this finding.

High prevalence of thrombophilic risk factors in patients with central retinal artery occlusion

IntroductionCentral retinal artery occlusion (CRAO) is a common cause of blindness and visual morbidity. In the majority of cases, it is related to thrombotic embolism. Nevertheless, the role of inherited or acquired thrombophilic risk factors in CRAO pathogenesis has not been comprehensively studied.MethodsIn 126 CRAO patients (66 [52.4%] men, median age 55 [range: 18–80] years) and 107 matched controls (56 [52.3%] men, median age 53 [range: 34–78] years) we evaluated classical atherosclerotic risk factors, including serum lipid profile and glucose level, analyzed intima-media complex thickness (IMT) of external carotid arteries, and performed transthoracic echocardiography. Furthermore, we established the prevalence of inherited and acquired thrombophilic risk factors, such as factor V Leiden (FVL) and prothrombin 20210 G/A genetic variants, plasma activity of factor (F) VIII, protein C and antithrombin activity, and free protein S levels. We also assessed the presence of antiphospholipid antibodies (APLA) and evaluated blood homocysteine in all enrolled subjects. Additionally, we estimated the occurrence of Val34Leu polymorphism of the A subunit of coagulation factor XIII (FXIII-A) in both groups as a potential thrombosis-protecting factor.ResultsAmong traditional atherosclerotic risk components, obesity/overweight and hypercholesterolemia were the most common in the CRAO group and occurred in 103 (81.7%) and 85 (67.5%) patients, respectively. CRAO patients also had elevated IMT and altered echocardiographic parameters, indicating diastolic cardiac dysfunction. In thrombophilia investigations, at least one laboratory risk factor occurred in 72.2% (n = 91) of CRAO patients, with APLA as the most frequent, detected in 38.1% (n = 48) of them (almost seven times more frequent than in controls, p < 0.001). Deficiencies in protein C activity and free protein S levels were also common in the CRAO group, reported in 17.5% (n = 22) and 19.8% (n = 25) of patients, respectively. Interestingly, among two analyzed prothrombotic genetic variants, only the FVL was related to CRAO, with the allelic frequency 2.4 times more prevalent than in controls (p = 0.044). Finally, the CRAO group was characterized by hyperhomocysteinemia, almost twice as common as in controls (p = 0.026). Antithrombin deficiency, elevated FVIII, and FXIII-A Val34Leu polymorphism were not associated with CRAO.ConclusionsOur findings suggest that thrombophilia plays a vital role in the pathogenesis of CRAO. Thus, proper laboratory screening should be considered in the primary and secondary prevention of those episodes, with implementing appropriate therapy as needed.

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.

Association between thrombophilia gene polymorphisms and recurrent pregnancy loss risk in the Iranian population

ABSTRACTMiscarriage is the most common complication in pregnancy. Considering the importance of the problem thrombophilia in pregnant women and its association with recurrent pregnancy loss (RPL), analysis of polymorphisms of genes involved in thrombophilia can be useful. We investigated the frequency and association between ten polymorphisms of seven thrombophilia genes and RPL in an Iranian population. This case-control study was conducted on 200 women with recurrent pregnancy loss and also on 200 women with at least one successful pregnancy as the control group. Using PCR-RFLP, DNA from samples were analyzed for carrying A5279G, A4070G, and FV Leiden of factor V; FXIII (Val34Leu); FII (A20210G); BF (−455 G⁄A); ITGB3 (1565T⁄C); 677C/T and 1298A/C of MTHFR; and PAI-1 (−675 I/D, 5G/4G) polymorphisms. The BF(−455 G⁄A), MTHFR (677 C⁄T, 1298A⁄ C), PAI-1 (−675 I/D,4G⁄ 5G), FV Leiden, FV (A5279G), FXIII (Val34Leu) polymorphisms, which had shown positive relation, and ITGB3 1565T⁄C were the polymorphisms with negative relation to RPL. But in this study it is indicated that there is no significant association between FII (A20210G) and FV (A4070G) polymorphism and RPL. All the data acquired from the RPL patients in this experiment illustrate the importance of screening thrombophilia. Nevertheless, more studies on large-scale populations may be needed to identify novel genetic variants.Abbreviations: ASRM: American Society of Reproductive Medicine; HHCY: hyperhomocysteinemia; MTHFR: methylenetetrahydrofolate reductase; PCR: polymerase chain reaction; PAGE: poly-acrylamide gel electrophoresis; RPL: recurrent pregnancy loss

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.

Blood coagulation factor XIII-A subunit Val34Leu polymorphisms and intracerebral hemorrhage risk: A meta-analysis of case-control studies

Background. Previous studies investigating the association between factor XIII-A subunit (FXIII-A) Val34Leu polymorphisms and intracerebral hemorrhage (ICH) had provided inconsistent results and no large systematic review or meta-analysis had been conducted regarding this issue. Methods. We conducted a meta-analysis to confirm whether the FXIII-A Val34Leu polymorphisms increased the risk of ICH. Relevant studies were identified from the Pubmed, Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases published up to September 2013. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for FXIII-A Val34Leu polymorphisms and ICH were calculated in a fixed-effects model or a random-effects model when appropriate. We also carried out the stratified analyses and sensitivity analyses by region, source of control group, and sample size. Results. Eight eligible studies were reviewed. As FXIII Val34Leu was absent or had a very low prevalence among East Asians, only six studies in Caucasians were analyzed, involving 564 cases and 1276 controls. Overall, the Leu allele of FXIII gene had a trend to slightly increased odds of having ICH, but there is no statistic significance (OR1.23, 95% CI 0.94–1.61, P = 0.13). The OR of genotypes Leu+(Leu/Leu or Leu/Val) for the risk of ICH was 1.21, 95% CI 0.98–1.50, P = 0.08. And the OR of recessive model genotypes was 1.53, 95% CI 0.81–2.88, P = 0.19. There was no difference of the association between the Leu allele of FXIII gene and risk of ICH in stratified analysis. Conclusions. Our meta-analysis suggests that there is no evidence for strong association between FXIII Val34Leu polymorphisms and ICH, but Leu allele of FXIII gene might slightly increase the risk of ICH in Caucasians. Since limited studies and subjects were included, larger scale association studies exploring the gene–gene interactions and gene–environment interactions are necessary to further validate the association.

Genetic association between FXIII and β-fibrinogen genes and women with recurrent spontaneous abortion: a meta- analysis.

FXIII Val34Leu (rs5985) and β-fibrinogen -455G/A (rs1800790) genotypes have been reported to be associated with recurrent spontaneous abortion (RSA). However, this topic is controversial. This study aimed to explore whether FXIII Val34Leu or β-fibrinogen -455G/A gene polymorphisms are related to RSA. In this analysis, PubMed, HuGENet and Chinese National Knowledge Infrastructure (CNKI) databases were reviewed. Four models including the dominant model (Val/Val+Val/Leu vs. Leu/Leu), recessive model (Val/Val vs Val/Leu + Leu/Leu), co-dominant model (Val/Val vs. Val/Leu, Val/Val vs. Leu/Leu) and per-allele analysis (Val vs. Leu) were applied. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the association between RSA and FXIII Val34Leu and β-fibrinogen -455G/A polymorphisms. Nine studies with 10 sets of data were included according to the inclusion criterion. A positive association was detected in the pooled results for the dominant model (Val/Val+Val/Leu vs. Leu/Leu; OR = 0.417, 95% CI: 0.180-0.965, I(2) = 45.60%) and co-dominant model (Val/Val vs. Val/Leu; OR = 0.638, 95% CI: 0.452-0.899, I(2) = 36.40%) for FXIII Val34Leu polymorphisms. However, no statistically significant association between β-fibrinogen -455G/A polymorphisms and RSA was detected in the four different models, including the Asian and Caucasian subgroup analyses. Our meta-analysis demonstrates that the FXIII Val34Leu polymorphism has a close association with RSA and women who carry the Val allele for the FXIII Val34Leu polymorphism could have a protective effect against RSA. However, no association is detected between β-fibrinogen -455G/A polymorphisms and the risk of RSA. Future well-designed studies are needed to confirm these results.

Factor XIII-A subunit Val34Leu polymorphism in fatal atherothrombotic ischemic stroke

Factor XIII (FXIII) is a regulator of fibrinolysis and clot firmness. Val34Leu polymorphism of its potentially active A subunit (FXIII-A) leads to faster activation of FXIII, influences clot structure and provides a moderate protection against coronary artery disease. The effect of FXIII-A Val34Leu polymorphism on the risk of atherothrombotic ischemic stroke (AIS) has been investigated in a few studies with contradictory results. In all previous studies, only patients surviving AIS were enrolled and sex-specific effects were not explored. In this retrospective multicenter cohort, we investigated the effect of FXIII-A Val34Leu polymorphism on the risk of fatal AIS in women and men. DNA isolation and genetic determinations in the case of 316 patients who died of AIS were carried out on paraffin-embedded tissue specimens. Genetic analyses for population controls, patients with history of AIS and sex-matched controls were performed on extracted genomic DNA from peripheral blood leukocytes. The prevalence of homozygous wild-type, and heterozygous genotypes, Leu34 carriers and Leu34 allele was not different significantly between the patients with fatal AIS and their respective controls. Logistic regression analysis with age as co-variant demonstrated that in women, homozygous presentation of Leu34 allele represented a more than three-fold increased risk of AIS with fatal outcome. The results demonstrate that FXIII-A Val34Leu polymorphism does not influence the occurrence of AIS, but has an effect on the severity of its outcome. This effect is sex-specific and in homozygous women, the prothrombotic/antifibrinolytic effects of FXIII-A Val34Leu polymorphism seem to prevail.

Effect of Factor XIII-A Val34Leu Polymorphism on Myocardial Infarction Risk

The association between factor XIII-A (FXIII-A) Val34Leu polymorphism and myocardial infarction (MI) risk remained controversial. We performed a meta-analysis. Online databases were searched. Twenty-eight studies were included. The FXIII-A Val34Leu polymorphism was significantly associated with MI risk (odds ratio (OR) = 0.83, 95% confidence interval [CI] 0.76-0.91; P < .0001). This result remained statistically significant when the adjusted ORs were combined (OR = 0.77, 95% CI 0.65-0.92; P = .004). When stratifying for race, this polymorphism showed decreased MI risk in Caucasians. In the subgroup analysis by age group, significant associations were observed in early-onset patients and in late-onset patients. In the subgroup analysis by gender, there was a significant association in women but not in men. In the subgroup analysis stratified by smoking status, MI risk was decreased in both smokers and nonsmokers. This study suggested that FXIIIA Val34Leu polymorphism was a protective factor for MI in caucasians.

Correlation of FXIII Val34Leu Polymorphism with Decreased Risk of Myocardial Infarction in Egypt

Correlation of FXIII Val34Leu Polymorphism with Decreased Risk of Myocardial Infarction in Egypt

Correlation of FXIII Val34Leu Polymorphism with Decreased Risk of Myocardial Infarction in Egypt

Aim: Factor XIII is a transglutaminase that crosslinks fibrin in the last steps of the coagulation process. A few polymorphic sites have been identified in this gene, one of them being a point mutation (FXIII Val34Leu), leading to an amino acid change of valine to leucine. Several studies were published on the association between FXIII 34Leu allele and a decreased incidence of myocardial infarction (MI) with high controversy results dependent on the population. The aim of our study was to further investigate the possible protective role of the FXIII 34Leu allele polymorphism against acute MI in Egyptian patients.

Factor XIII A subunit Val34Leu polymorphism in patients suffering atherothrombotic ischemic stroke

IntroductionFactor XIII (FXIII) is a key regulator of fibrinolysis and clot firmness. Val34Leu polymorphism of its potentially active A subunit (FXIII-A) leads to faster activation of FXIII, influences clot structure and provides a moderate protection against coronary artery disease. The effect of FXIII A subunit (FXIII-A) Val34Leu polymorphism on the risk of ischemic stroke (IS) has been investigated in a few studies with contradictory results. In spite of their fundamental difference in pathogenesis and hemostatic pathomechanism, only four small studies investigated the effect of FXIII-A Val34Leu polymorphism on the risk of atherothrombotic IS (AIS) separately from cardioembolic IS. Gender specific effect of the polymorphism on the risk of AIS has not been explored. In the present study we investigated the effect of FXIII-A Val34Leu polymorphism on the risk of AIS on a large patient population. Materials and methodsA population control group of 1,146 randomly selected individuals, 496 patients surviving AIS and their age and sex-matched controls selected from the population control group were included in the study. FXIII-A Val34Leu genotype was determined on DNA samples, obtained from peripheral blood leukocytes, by fluorescence resonance energy transfer detection using melting curve analysis. ResultsNeither sex nor age affected the distribution of FXIII-A Val34Leu genotypes in population control group. No association was revealed between the risk of AIS and FXIII-A Leu34 carriership and homozygous or heterozygous presentation of Leu34 allele in either gender. ConclusionFXIII-A Val34Leu polymorphism fails to influence the risk of AIS.

The inflammatory response is influenced by FXIII VAL 34 LEU polymorphism in a human LPS model

In sepsis, activation of coagulation and inhibition of fibrinolysis lead to microvascular thrombosis. The Val34Leu polymorphism affects the function of FXIII by increasing the rate of FXIII activation by thrombin, which results in an increased and faster rate of fibrin stabilization. Sepsis and multi-organ failure cause disturbance of the normal balance of inflammation and coagulation, one of the most frequent causes of death in ICU patients. Research in polymorphism has shown the possible influence of FXIII in coagulation and inflammation. We analyzed the influence of the common FXIII Val34Leu polymorphism on inflammatory and coagulation parameters in human experimental endotoxinemia. Healthy volunteers (n = 62) received 2 ng endotoxin (LPS) per kg body weight as a bolus infusion over 2 min. We developed a new mutagenic separated PCR assay for determination of the FXIII promoter polymorphism. FXIII levels were higher for homozygous carriers of the FXIII polymorphism in comparison with wild-type 34 Val/Val and heterozygous 34 Val/Leu. Interestingly, persons homozygous for the FXIII Val34Leu polymorphism had lower monocyte and neutrophil counts throughout the observation period, yet prothrombin fragment 1+2 and D-dimer levels did not differ after LPS challenge. Our findings indicate that the common FXIII Val34Leu polymorphism is associated with differences in monocyte and neutrophil cell counts in response to systemic LPS infusion in humans.

Impact of hemostatic gene single point mutations in patients with non-diabetic coronary artery disease

Single point mutations in the genes coding for hemostatic factors were shown to be major inherited predisposing factors for venous thromboembolism. However, their contribution in the development of non-diabetic coronary artery disease [nDCAD] remains controversial. Angiographically demonstrated nDCAD patients (n = 86) and healthy controls (n = 90) were included in the study. Genotype analysis of hemostatic gene polymorphisms were assessed by using CVD strip assay, based on allele specific oligonucleotide probes. The carrier frequency of factor V (FV) H1299R, prothrombin G20210A, glycoprotein (Gp) IIIa L33P, plasminogen activator inhibitor-I (PAI-1) 4G/5G, 4G/4G, 5G/5G, methylenetetrahydrofolate reductase (MTHFR) A1298C and beta-fibrinogen -455 G > A were similar between patients and controls. In contrast, frequency of FV Leiden was significantly higher among patients (12.5%) than controls (5%, OR: 7.94; 95%CI: 1.9-49.6) and FXIII V34L was significantly lower among patients (23.7%) than controls (40%, OR: 0.24; 95%CI: 0.1-0.89). In addition, the frequency of the MTHFR C677T polymorphism was 32.5% among patients compared with 42.5% in controls, of which the T/T genotype was significantly lower among patients (5%) than controls (17.5%, OR: 0.06; 95%CI: 0.01-0.58). No difference was observed in prevalence of prothrombin G20210A, FV H1299R, Gp IIIa L33P, PAI-1 4G5G, MTHFR A1298C, beta fibrinogen 455 G > A mutations between patients and controls. However, lower frequency of FXIII Val34Leu and MTHFR C677T polymorphisms may decrease, while FV Leiden polymorphism may increase development of nDCAD.

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

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.

Impact of FXIII-A Val34Leu polymorphism on coronary artery disease in Croatian patients

Arterial thrombosis is the major reason for severe complications of coronary artery disease (CAD). Recently it has been suggested that the FXIII-A Val34Leu polymorphism, affecting clot stability, provides protection against thrombosis. Results published up to date implicate that there is a significant correlation between geographical area and the Leu34 allele prevalence and that its contribution to arterial thrombosis is different in different populations. The purpose of this study was to determine frequency of Leu34 allele in Croatian subjects as well as to estimate its association with a CAD. FXIII-A Val34Leu genotyping was carried out by real-time PCR method on the LightCycler using melting curve analysis with forward 5'-AACTTCCAGGACCGGCTTT-3' and reverse 5'-ACCCAGAGTGGTGGGGAA-3' primers. The Leu34 allele frequency in studied Croatian subjects was 24.3%. No significant differences were found in the prevalence of FXIII-A Val34Leu genotype or Leu34 allele distribution between studied subjects (P > 0.05). Carriage of the Leu34 allele was not significantly associated with CAD or MI risk reduction (P > 0.05). This is the first report that studies the prevalence of the Leu34 allele frequency in Croatian subjects and our results suggest that possession of the Leu 34 alele does not provide protection against MI.

Decreased factor XIII levels in factor XIII A subunit Leu34 homozygous patients with coronary artery disease

Introduction The effect of factor XIII A subunit (FXIII-A) Val34Leu polymorphism on the risk of coronary artery disease (CAD) has been extensively studied. In this study we investigated how FXIII-A Val34Leu genotypes influence plasma factor XIII levels in patients with coronary sclerosis (CS) and myocardial infarction (MI) and how fibrinogen level modulates this effect. Patients and methods 955 consecutive patients admitted for coronary angiography were categorized according to the presence or absence of significant CS and the history of MI. The frequency of FXIII-A Val34Leu polymorphism, fibrinogen, FXIII activity and antigen levels were determined. Results and conclusions CS or MI decreased FXIII levels in patients homozygous for FXIII-A Leu34 allele, but not in heterozygous or wild type patients. In the subgroup of patients with CS, but without the history of MI no significant effect was detected, which suggests that MI has a more prominent role. The specific activity of plasma FXIII was independent of FXIII-A Val34Leu genotype. FXIII and fibrinogen levels significantly correlated in CS+ and MI+ patients. In MI+ patients of Leu/Val or Leu/Leu genotypes and with fibrinogen levels in the lowest quartile, FXIII levels were lower than in the same patient groups, but with higher fibrinogen level. The low-scale continuous activation of blood coagulation in CAD patients could lead to parallel FXIII and fibrinogen consumption. As the same amount of thrombin activates more Leu34 FXIII than Val34 FXIII, increased FXIII consumption might be responsible for the decreased FXIII levels in Leu34 homozygous CAD patients.

Fibrinogen Aα-Thr312Ala and factor XIII-A Val34Leu polymorphisms in idiopathic venous thromboembolism

Introduction Fibrinogen Aα-Thr312Ala and Factor XIII Val34Leu polymorphisms have been shown to modify fibrin clot structure and function. However, clinical studies have yielded conflicting results on their possible association with venous thromboembolism (VTE). Methods We studied the association between these two polymorphisms and VTE in a hospital-based case–control study. We also assessed whether an independent or interactive association exists between Aα-fibrinogen Thr312Ala and FXIII Val34Leu polymorphisms and VTE. Fibrinogen Aα-Thr312Ala and FXIII Val34Leu polymorphisms were determined after PCR and restriction endonuclease digestion in 286 patients with idiopathic VTE and 286 age- and gender-matched controls. Results were analysed using a conditional logistic regression model for matched series. Results The Fg-Aα 312Ala allele was associated with higher risk of VTE (OR 1.5; 95% CI: 1.1 to 2.2, p=0.01) while the FXIII 34Leu allele appeared protective (OR 0.7; 95% CI: 0.6 to 0.9, p=0.02). Both alleles demonstrated an independent association with idiopathic VTE after adjustment for Factor V Leiden and G20210A prothrombin polymorphisms. There was no interaction between the fibrinogen Aα-Thr312Ala and FXIII Val34Leu polymorphisms for the risk of VTE. Conclusion In this case-control study, the fibrinogen Fg-Aα 312Ala allele was associated with an increased risk of VTE. The FXIII 34Leu allele was also significantly associated with a lower risk of VTE without any interaction between the two polymorphisms studied.

Modulation of the risk of coronary sclerosis/myocardial infarction by the interaction between factor XIII subunit A Val34Leu polymorphism and fibrinogen concentration in the high risk Hungarian population

Introduction The results on the association of factor XIII (FXIII) A subunit (FXIII-A) Val34Leu polymorphism with the risk of myocardial infarction (MI) are rather inconclusive. The original paper and confirmatory reports demonstrated a protective effect of the mutation, but results demonstrating the lack of protection have also been published. Gene–gene and gene–environmental interactions have been proposed to be responsible for the opposing results. As the rate of change in fibrin clot permeability with increasing fibrinogen concentrations decreased stepwise with increasing number of Leu34 alleles it was proposed that the protection by Val34Leu polymorphism become effective only at higher fibrinogen concentrations. However, this hypothesis has not been tested on patients with coronary artery disease. Patients and methods 955 consecutive patients admitted for coronary angiography were categorized according to the presence or absence of significant coronary sclerosis (CS) and according to positive or negative history of MI. The frequency of FXIII-A Val34Leu polymorphism, and a number of risk factors, including fibrinogen were determined in the patients. FXIII-A Val34Leu polymorphism was also investigated in a population control group of 1146 subjects. Results The presence of FXIII-A Leu34 allele or homozygous Leu34 genotype did not change the risk of CS or MI in the general Hungarian population. However, when patients with fibrinogen level in the upper quartile were separately investigated, the Leu34 allele provided a statistically significant protection against MI. Conclusions Fibrinogen concentration modulates the effect of Leu34 allele on the risk of MI; its protective effect emerges at increasing fibrinogen concentration.

Factor XIII Val34Leu variant protects against coronary artery disease

Several studies suggested that Val34Leu variant of factor XIII (FXIII) might have a protective effect against coronary artery disease (CAD), but studies not supporting these findings have also been published. The authors performed a meta-analysis of 16 studies on 5,346 cases and 7,053 controls that investigated the association between Val34Leu polymorphism and CAD defined as history of myocardial infarction or significant stenosis on a coronary artery assessed by coronary angiography. Because of the heterogeneity of the study-specific results, the pooled effect estimates were calculated by a random-effects empirical Bayes model. The combined odds ratios for CAD were 0.82 (95% confidence interval [95% CI] 0.73, 0.94) for the heterozygotes of the FXIIIVal34Leu variant, 0.89 (95% CI 0.69, 1.13) for the homozygotes, and 0.81 (95% CI 0.70, 0.92) for the heterozygotes and homozygotes combined. The results were essentially the same when only myocardial infarction was considered as outcome. The beneficial effect of the polymorphism might be smaller than the effect estimates obtained in this meta-analysis, because the analysis raised the possibility of publication bias. Data published in the literature suggest that gene-gene and gene-environmental interactions might significantly influence the protective effect of FXIII-A Val34Leu polymorphism.