Leiden G1691A Research Articles

Assessment of Genetic Variants Linked to Susceptibility to Mechanical Prosthetic Valve Thrombosis

Prosthetic valve thrombosis (PVT) is a critical and life-threatening condition, driven by multifactorial etiologies including genetic predispositions. The study was designed as a single-center retrospective manner. Echocardiographic features and genetic test including Factor II Prothrombin G20210A, Factor V Leiden G1691A, Factor V R2 A4070G, ApoB-100 G10708A, ApoE C112R, ApoE R158C, MTHFR C677T, MTHFR A1298C, Factor XIII G103T (V34L), Beta fibrinogen G-455A, PAI-1 4G/5G, and HPA-1 (GPIIIa) T196C genotyping variations were assessed. We performed genetic tests in 175 patients with PVT [biologically women (n=124, 70.9%) with a mean age of 49.8 ± 13.1 years], and in 101 patients [biologically women (n=57, 56.4%) with a mean age of 54.7 ± 13.6 years] without thrombus formation. The thrombosis group was significantly younger compared to controls (p=0.004). The percentage of patients with mechanical aortic valves was significantly lower in the thrombosis group compared to controls (22.3 vs 34.7%, p=0.025). A significant difference was observed between the thrombosis and control groups regarding the genotype ratios of Factor II/Prothrombin (G20210A) (heterozygous, 6.8 vs 1%, p =0.043) and HPA-1 GPIIIa (T196C) (homozygous mutant, 7.8 vs, 0%, p=0.034) In addition, there was a significant association of heterozygous MTHFR (A1298C) variation with obstructive thrombosis compared to non-obstructive thrombosis (46.9 vs 29.2%, p=0.046). In conclusion, this is the first study to report a potential association between genetic variants including HPA-1 GPIIIa (T196C), Factor II/Prothrombin (G20210A), MTHFR (A1298C) and PVT, necessitating extensive further research and additional clinical consideration.

Factor V Leiden G1691A, Prothrombin G20210A, and MTHFR C677T Mutations among Sudanese Women with Recurrent Pregnancy Loss

Background: Various factors, such as genetic causes, anatomic abnormalities of the uterus, infectious diseases, coagulative disorders, and endocrinological and immunological diseases, might influence recurrent pregnancy loss (RLP). This study aimed to evaluate the prevalence and frequency of the FII G20210A, FVL G1691A, and MTHFR C677T polymorphisms in Sudanese women with RPL. Methods and Results: This descriptive cross-sectional study involved 100 women with a history of 3 or more RPLs (the case group) and 94 healthy multiparous women without pregnancy complications (the control group). DNA was extracted from peripheral blood samples. The study of the FII G20210A, FVL G1691A, and MTHFR C677T polymorphisms was performed by PCR and RFLP analysis. For the FII G20210A, the genotype distribution in the case group and control group was as follows: GG=97.0%, GA=3.0%, AA=0% and GG=94.0%, GA=0%, AA=0%, respectively. In the case group, the allelic distribution was as follows: G=98.5%, A=1.5%. In the control group, the A allele was absent, and the frequency of the G allele was 100%. For the MTHFR C677T, the genotypic and allelic frequencies in the case group were 97%, 3%, and 0%, respectively, for the CC, CT, and TT genotypes, and 98.5% and 1.5%, respectively, for the C and T alleles. In the control group, the genotype distribution was as follows: CC-100% CT-0%, TT-0%; the T allele was absent, and the frequency of the C allele was 100%. For the FVL G1691A, the genotype distribution in the case group and control group was as follows: GG=92.0%, GA=8.0%, AA=0% and GG=93.6%, GA=6.4%, AA=0%, respectively. For G and A alleles, the frequencies were 96.0% and 4.0%, respectively, for the case group, and 96.8% and 3.2%, respectively, for the control group. Our analysis did not reveal a significant positive association between the MTHFR C677T, FII G20210A, and FVL G1691A polymorphisms and the risk of RPL across the dominant model, multiplicative model, and a comparison of the frequencies of the heterozygous and homozygous dominant genotypes. Conclusion: The research findings suggest that the MTHFR C677T, FVL G1691A, and FII G20210A variants do not significantly contribute to the increased susceptibility to RPL in this specific population of Sudanese women. Continued scientific inquiry is crucial for developing more nuanced and personalized strategies for the diagnosis and prevention of RPL, ultimately improving women's reproductive health.

The Impact of Thrombophilic Factors on Disease Progression in Children with Biliary Atresia-A Single-Centre Cohort Study.

Epidemiological evidence suggests that thrombophilic factors, including male sex, non-O blood type, MTHFRnt677TT mutation, factor V Leiden G1691A mutation, and prothrombin G20210A polymorphism, may contribute to the progression of fibrosis and occurrence of portal vein thrombosis in liver disease. We retrospectively investigated the effect of potentially thrombophilic factors on native liver survival as a patient-relevant endpoint of disease progression in a cohort of 142 children being followed up for biliary atresia at Hannover Medical School from April 2017 to October 2019. No significant association could be determined. There was no evidence for relevant differences in native liver survival for the Factor V Leiden G1691A mutation (hazard ratio [HR] = 0.86, 95% confidence interval [CI] 0.38-1.98, p = 0.73), prothrombin G20210A polymorphism (HR = 0.96, 95%CI 0.24-3.65, p = 0.96), non-O blood type (HR = 0.79, 95%CI 0.51-1.21, p = 0.28) or MTHFRnt677TT mutation (HR = 1.24, 95%CI 0.60-2.56, p = 0.56). A certain, albeit not strong, evidence of reduced native liver survival in male patients after Kasai hepatoportoenterostomy, particularly during the first 2000 days (42%; HR = 1.41, 95%CI 0.92-2.18, p = 0.11) was found. All children with pre-transplant portal vein thrombosis (n = 7) had non-O blood types. Larger multi-centre studies are necessary to show if the male sex or other thrombophilic factors could be potentially associated with reduced native liver survival.

Methylenetetrahydrofolate Reductase 677T Allele Is a Risk Factor for Arterial Thrombosis in Chinese Han Patients with Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by the persistent presence of antiphospholipid antibodies (aPL) and thrombotic or obstetric events. Given the heterogeneity of the clinical manifestations, it is likely that genetic and acquired factors are involved in the pathogenesis of APS. The inherited polymorphisms of the thrombophilic gene, including methylenetetrahydrofolate reductase (MTHFR) C677T, type 1 plasminogen activator inhibitor (PAI-1) 4G/5G, factor V Leiden (FVL) G1691A, prothrombin (PT) G20210A, antithrombin (AT), and fibrinogen (Fg) polymorphisms, were analyzed in 67 aPL(+) patients from the Chinese Han population, including 41 APS patients and 26 persistent aPL carriers. The MTHFR C677T genotypes of 105 healthy controls, and the PAI-1 4G/5G polymorphism of 120 healthy controls, from the Chinese Han population were acquired for this study. Both the MTHFR C677T genotype (χ2 = 10.67, p = 0.004) and C/T allele distribution (χ2 = 5.92, p = 0.019) between the aPL(+) patients and healthy controls were found to be significantly different. Furthermore, we observed that the patients with at least one T allele had a higher risk of arterial thrombosis (CT vs. CC, OR 11.00, p= 0.025; CT + TT vs. CC, OR 10.27, p = 0.018). The C677T mutation of MTHFR is a risk factor for arterial thrombosis in Chinese Han patients with APS.

Possible effect of genetic background in thrombophilia genes on clinical severity of patients with coronavirus disease-2019: A prospective cohort study

Background and objective: Thrombotic and microangiopathic effects have been reported in Coronavirus Disease-2019 (COVID-19) patients. In the present study, we aimed to examine the relationship between hereditary thrombophilia factors and the clinical picture severity of COVID-19 patients. Methods: Ninety COVID-19 patients were included and grouped according to the severity to three groups: severe/critical (n=30), mild/moderate (n=30) and asymptomatic (n=30). Hereditary thrombophilia genetic markers [prothrombin (FII) G20210A, factor V Leiden (FVL) G1691A, factor XIII (FXIII) V34L, methylene tetrahydrofolate reductase (MTHFR) A1298C and C677T, and plasminogen activator inhibitor-1 (PAI-1) 4G & 5G] were genotyped for all patients. Results: Seventeen (18.9%) patients had the polymorphism 4G/4G PAI-1 and 48 (53.3%) had 4G/5G. In addition, the heterozygous GA FVL, MTHRF677CT, and MTHRF1298AC polymorphisms were detected in 11 (12.2%), 26 (28.9%), and 38 (42.2%) patients, respectively. The rate of severe/critical patients with PAI 4G/5G gene polymorphism was higher than the asymptomatic+moderate/mild patients, and the rate of severe/critically ill patients with PAI 4G/4G polymorphism was found to be lower than the asymptomatic+moderate/mild patients. No difference was evidenced between the distribution of deceased and survivors of the genotype groups. Conclusions: In the present study, we found that heterozygous 4G/5G PAI-1 polymorphism is associated with critical or severe COVID-19 picture, and that FVL, MTHFR, FXIII, and prothrombin polymorphisms were not directly related to COVID-19 severity.

Analysis of polymorphisms in recurrent pregnancy loss: Factor V Leiden G1691A, Factor II G20210A, MTHFR C677T and Factor V H1299R

The distribution of factor V Leiden G1691A, factor II G20210A, MTHFR C677T, and factor V H1299R polymorphisms known to predispose to thrombophilia in 215 cases and 40 controls admitted with indication of recurrent pregnancy loss (RPL) was investigated. Genotyping was performed by melting curve analysis using simultaneous PCR (RT-PCR). There was no difference between genotype and allele frequencies in the case and control groups in terms of the polymorphisms examined (p>0.05). In the genotype distribution of the Factor V gene G1691A polymorphism, 12.6% GA in the case group and 90.0% GG (wild) genotypes in the control group were found to be higher than the other genotypes. In the genotype distribution of the factor II gene G20210A polymorphism, the GG (wild) genotype was found to be higher in 94.5% and 97.5%, respectively, in the case group and control group than the other genotypes. In the genotype distribution of MTHFR gene C677T polymorphism, 43.7% CC (wild) in the case group and 40.0% CT genotype in the control group were found to be higher than the other genotypes. In the genotype distribution of the factor V gene A4070G polymorphism, 87.4% AA (wild) in the case group and 80% AA (wild) genotype in the control group were found to be higher than the other genotypes. However, the frequency of risk allele A for factor V Leiden G1691A (6.8% and 5%), the frequency of risk allele A for factor II gene G20210A (3% and 1.2%), MTHFR gene C677T were determined in the case and control groups. The frequency of the T allele (35.9% and 42.5%), which is the risk allele for A4070G, and the frequency of the G allele (6.5% and 16.6%), which is the risk allele for the factor V gene A4070G, were determined. When our study results were evaluated, no relationship was found between RPL and factor V Leiden G1691A, factor II G20210A, MTHFR C677T, and factor V A4070G polymorphisms.

Impact of Factor V Leiden G1691A, MTHFR C677T, and Prothrombin G20210 A mutations on the development of neonatal thrombosis

Impact of Factor V Leiden G1691A, MTHFR C677T, and Prothrombin G20210 A mutations on the development of neonatal thrombosis

Detection of factor V G1691A, Prothrombin G20210A and Methylene tetra hydro folate reductase deficiency C677T Gene mutations among Sudanese Women with recurrent spontaneous abortion

The current study is a prospective analytical case control study designed to investigate the relationship between Factor V Leiden G1691A, methylenetetrahydrofolate reductase (MTHFR) C677T and to the prothrombin G20210A mutation variant and adverse pregnancy outcomes. Material and Method: The study included hundred Sudanese women who experienced three or more of the adverse pregnancy loss as case group during their reproductive in the Omdurman Maternity Hospital (Sudan) these compared with ninety-four control group healthy women with at least more than two normal pregnancies and without any history of adverse pregnancy outcome or recurrent miscarriages. The study group data collected using structure questionnaire which was used to collect information about age, parity, medical and obstetric history, smoking, family medical and obstetric history, residency and relative marriage. Blood samples were collected from participants and total genomic DNA was isolated from blood leukocytes and the frequency of these gene mutations in the patients and controls were determined using PCR-restriction fragment length. Results the mutation was detected in 8 out of 100 cases (8.0%) and in 6 out of 94 controls (6.4%) (P- Value > 0.05).

MTHFR C677T (rs1801133) genetic polymorphism is associated with development risk of essential hypertension in the Turkish population

BackgroundHypertension is a serious condition that is spread worldwide and may lead to severe complications such as heart attack, stroke, hypertensive retinopathy, and renal failure. Although some genetic and environmental risk factors are known to play a role in the etiology of hypertension, like most of the other multi-factorial diseases, its etiology is yet to be fully elucidated. Our study aimed to investigate the effects of methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) and A1298C (rs1801131), factor V Leiden (FVL) G1691A (rs6025), and prothrombin (PT) G20210A (rs1799963) genetic polymorphisms on the development risk of essential hypertension and level of blood pressure in hypertensive patients.ResultsThe frequency of the homozygous polymorphic TT genotype for the MTHFR C677T polymorphism was significantly higher in male hypertensive patients than in the male control group (27% vs 6.3%, p = 0.028). The rate of the variant T allele for the MTHFR C677T polymorphism was also significantly higher in male hypertensive patients compared to male healthy controls (51.4% vs 21.9%, p = 0.0004). There was no difference among hypertensive patients and healthy controls regarding the frequencies of MTHFR A1298C, FVL G1691A and PT G20210A polymorphisms. In addition, we found no difference between genotype groups regarding systolic and diastolic blood pressure levels in hypertensive patients.ConclusionsHomozygous polymorphic TT genotype and variant T allele for the MTHFR C677T polymorphism may be considered as a risk factor for the development of essential hypertension in the Turkish male population.

Simultaneous and sensitive detection of two pathogenic genes of thrombotic diseases using SPRi sensor with one-step fixation probe by a poly-adenine oligonucleotide approach

Single-base mutations of Factor V Leiden G1691A and Prothrombin gene G20210A are the main genetic risk factors for inherited thrombotic tendency. The establishment for rapid and efficient detection method is of great significance to the prevention of venous thrombosis. In this work, a multiplexed, highly sensitive and regenerable surface plasmon resonance imaging (SPRi) sensor is described to identify and detect the two pathogenic genes by fixing probes in one-step. The probes are fixed by ployA, which is a simpler, faster and lower cost modification method compared with traditional thiol (-SH). PolyA-DNA-AuNPs is used to amplify the signal to improve sensitivity. The detection limit of the sensor is 8 pM, and it has a wide dynamic range between 8 pM and 100 nM and a good linear relationship between 8 pM to 50 pM. The equilibrium dissociation constant (KD) of 3.0 (± 0.3) pM indicates a high binding capacity. Based on the advantages of high-throughput detection, the SPRi chip can simultaneously identify and detect two genes related to thrombotic Diseases. In addition, more than 90% signal intensity can still be obtained on the surface of the chip after being regenerated of 25 times, indicating that this SPRi sensor has good stability and reproducibility. The established SPRi sensor has the advantages of high-throughput, high-sensitivity, label-free and no need for amplification, which is expected to become an effective technical means for real-time online detection of gene point mutations, and can be extended to detect and quantify a wider range of DNA mutation diseases.

Impact of thrombophilia and waist circumference on the risk of venousthromboembolism

Abstract Background Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE) represents a major health problem. In the general population, the absolute risk of any kind of VTE is 0.1%–0.2% per year, and it increases with age. VTE is an important and preventable cause of morbidity and mortality, with almost a third of survivors experiencing long term effects. Obesity is well-known risk factor of VTE. The extent of the effects of obesity on VTE depends not only on total body fat, but also on the distribution of adipose tissue (e.g., central obesity) and the interplay among risk factors for VTE, such as genetic mutations, and other risk factors. Thrombophilia, venous thromboembolism, obesity, waist circumference Purpose The aim of this study is to investigate the impact of waist circumference on the risk of venous thromboembolism Methodology The study involved 68 patients with VTE (33 females and 34 males, mean age 56.8 years ±15.3) and 84 patients without VTE (38 males and 46 females, 44.4 years±18.6). From 2015 to 2017, data have been collected from records of patients admitted to department of internal medicine. All subjects were recruited to the study during their stay in the hospital. The reasons for hospitalization were: acute event of DVT or PE for the main group, the absence of acute event or history of VTE for the control group. DVT was diagnosed by ultrasonic Doppler examination, and PE was confirmed by intravenous radiocontrast computed tomography. Anthropometric measures were performed with subjects wearing short-sleeved garments and no shoes; waist circumference was measured in centimeters at the umbilical line. For all patients genetic testing for inherited thrombophilia – Factor V Leiden G1691A, Prothrombin G20210A, MTHFR C677T polymorphism, PAI-1 (SERPIN1) 4G/5G polymorphism – was performed by real-time PCR technique. Results Factor V Leiden G1691A increase the risk of VTE in 2.11 (CI: 1.79–2.48), p=0.049, prothrombin G20210A in 3.21 (CI: 1.66–6.211), p=0.049. MTHFR C677T polymorphism, PAI-1 (SERPIN1) 4G/5G polymorphism also increase the risk of VTE, but it was no significant. Study have shown that waist circumference >80 cm increase the risk of VTE in 3.19 (CI: 1.35–7.58), p=0.019. Combination of inherited thrombophilia (Factor V Leiden G1691A, Prothrombin G20210A, MTHFR C677T polymorphism, PAI-1 (SERPIN1) 4G/5G polymorphism) and waist circumference >80 cm increase the risk of VTE in 3.51 (CI: 1.76–7.04), p<0.001. Conclusion Previous results of our work indicate influence of waist circumference >80 cm on the risk of VTE, especially risk of thrombosis is higher in patients with combination inherited thrombophilia and waist circumference >80 cm. Funding Acknowledgement Type of funding sources: None.

Hereditary thrombophilia and adverse pregnancy outcomes

Background: Multiple studies have found a relatively increased risk of placenta-mediated pregnancy complications in women with congenital thrombophilia, especially early recurrent pregnancy loss, fetal loss, early-onset preeclampsia, intrauterine growth restriction, and premature abruption of normally positioned placenta. However, the extent of the association and the absolute risk are very modest, but they significantly increase in pregnant women with severe obstetric complications. Conclusions: There is convincing evidence that deficiency of natural anticoagulants (antithrombin, protein C, protein S) is a risk factor for late fetal loss. Factor V Leiden G1691A gene mutation and prothrombin G20210A gene mutation are associated with a double risk for early and unexplained recurrent pregnancy loss and for non-recurrent late fetal loss. The association of congenital thrombophilia with preeclampsia is much more uncertain, being probably limited factor V Leiden G1691A gene mutation and more severe cases of preeclampsia. Fewer data are available on intrauterine growth restriction (IUGR) and premature abruption of the normally positioned placenta. There is insufficient evidence to suggest an association of other forms of congenital thrombophilia with adverse pregnancy outcomes. In addition, genetic and epidemiological research suggests that placenta-mediated pregnancy complications are of polygenic multifactorial etiology, with a risk determined by the interaction of multiple genetic variants and other risk factors.

Prevalence of Factor V Leiden G1691A and Prothrombin G20210A Gene Mutation Among Pregnant Women: Experience from a Multi-Center Study in Nigeria.

IntroductionInherited thrombophilia and venous thromboembolism (VTE) have been closely linked to adverse pregnancy outcomes such as preeclampsia/eclampsia contributing to increased maternal and perinatal morbidity and mortality. There is, however, little genetic data from Africa including Nigeria that explores the prevalence of common VTE genetic risk markers such as factor V Leiden mutation (FVL G1691A) and prothrombin gene mutation (F2 G20210A) among pregnant women in Nigeria.PurposeTo determine the prevalence and distribution of FVL G1691A and F2 G20210A in pregnant women in Lagos, Nigeria.Patients and MethodsThis hospital-based cross-sectional pilot study was conducted among pregnant women between 1 July 2019 and 31 August 2020. The genotype of interest was determined through amplification by polymerase chain reaction using G1691A of FV and prothrombin A20210G specific primers. Descriptive data were presented using Stata version 15 (Stata Corp) statistical software.ResultsOf the 400 recruited participants, 397 and 389 samples were successfully processed for FVL G1691A and F2 G20210A mutations, respectively. Three participants had FVL heterozygous mutation; thus, the prevalence of heterozygous mutation of FVL among the study participants was 0.76%, 95% CI: 0.002–0.023%, n=3/397. There was no F2 G20210A mutation detected among the study participants.ConclusionThis study indicates that screening for factor V Leiden mutation and prothrombin gene mutation in pregnancy might not be of any clinical significance among Nigerian women. However, carrying out a genome-wide associated study is recommended to determine the true impact of these two common inherited thrombophilias in this population.

Evaluation of pai-1 polymorphisms in central and peripheral thromboembolies

Thromboembolism is a clinical finding that occurs due to thrombus; formed in the vascular system and has various etiological factors. It can be classified as central and peripheral thromboembolism. Our objective in this study is to explore genetic risk factors in central and peripheral thromboembolism and reveal the differences. 342 thromboembolism patients were retrospectively included to the study between January 2016 and December 2019. Demographic characteristics, risk factors for thromboembolism and genetic mutations in central and peripheral thromboembolism groups were overviewed. The genetic mutations evaluated in patients were Factor V Leiden G1691A, Factor V HR1299R, Factor II (Prothrombin) G20210A, MTHFR (Methylenetetrahydrofolate reductase) C677T, MTHFR A1298C, PAI 4G/5G. Within the scope of the study, genetic analyzes of 106 patients were reached and included in the study. Seventy-two central thromboembolism (69.8%), 34 (31.2%) peripheral thromboembolisms were detected. Sixty-three of the central thromboembolisms were from arterial and nine were from venous origin. There was no significant difference between age, gender and risk factors of central thromboembolism and peripheral thromboembolism patients (p˃0.05), but smoking was more common in central thromboembolism patients (p: 0.041). 4G/5G polymorphism was observed more frequently in patients with central thromboembolism (p: 0.039). Thromboembolism is a multifactorial disease, PAI-1 4G/5G polymorphism is a medium risk factor for thromboembolism. We conclude that PAI-1 4G/5G polymorphism is more frequent in central thromboembolism than peripheral thromboembolism and its evaluation can give more information about the thromboembolic risk analyze.

Frequency of hereditary prothrombotic risk factors in patients with Down Syndrome

Objective: Down Syndrome (DS) is defined as chromosome 21 trisomy and associated with cardiovascular system diseases. We aimed to study inherited thrombophilia genes (MTHFR A1298C, MTHFR C677T, Factor II G20210A, Factor V Leiden G1691A, Factor V Cambridge G1091C, Factor XIII, APOB, ITGB3, FVHR2, FGB, PAI-1 and ACE) in patients with DS. Materials and Methods: A total of 53 patients with DS (32 male and 21 female) were included in the study. Demographical, laboratory and clinical features of cases were recorded. 12-lead Electrocardiogram (ECG), transthoracic echocardiography and the inherited thrombophilia genes were evaluated. Results: The clinical and developmental defect findings of the patients were high. The 39.6% of patients had both heterozygous MTHFR C677T and heterozygous MTHFR A1298C carriers, the 18.9% of patients had homozygous MTHFR A1298C carriers, the 17% of patients had heterozygous Factor V Leiden G1691A carriers, the 43.4% of patients had 4G/4G carriers, the 34% of patients had 4G/5G variation carriers for PAI, the 22.7% of patients had heterozygous FactorXIII carriers, the 49.1% of patients had ins/del carriers and the 37.7% of patients had del/del variation carriers for ACE. All patients had at least one of the homozygous and/or compound heterozygous variations for the inherited thrombophilia. Conclusions: The patients with DS have a high risk for thrombosis-related cardiovascular system diseases. It may be said that the average life expectancy of individuals with DS may be increased by precautions (related to medical, social, lifestyle, etc.) to reduce complications associated with hereditary thrombophilia.

Association of Factor V Leiden G1691A and Prothrombin gene G20210A mutations with adverse pregnancy outcomes.

To determine the association of Factor V Leiden / prothrombin gene mutation in Pakistani women with adverse pregnancy outcomes. The prospective study was conducted at the Aga Khan University Hospital, Karachi, from January 1 to December 31, 2016, and comprised females > 40 years having history of two or more foetal losses with no apparent aetiology. Restriction fragment length polymorphism- Polymerase chain reaction was performed using MnlI and HindIII restriction enzymes for factor V Leiden G1691A and prothrombin gene mutation G20210A. Females with two or more consecutive normal pregnancies were enrolled as the control group. Data was analysed using SPSS 19. Of the 172 participants with a mean age of 29.3±5.9 years (range: 19-38 years). 86(50%) each were healthy controls and those with recurrent pregnancy loss. There were 238 livebirths among the controls compared to 13 in the other group. Factor V Leiden G1691A was identified in 2(2.3%) women, and prothrombin gene mutation G20210A in 1(1.2%) woman in the patient group, while no mutation was identified in the control group. The prevalence of Factor V Leiden / prothrombin gene mutation in women with recurrent pregnancy loss was found to be very low.

Association of venous thromboembolism and myocardial infarction with Factor V Leiden and Factor II gene mutations among Libyan patients

ABSTRACT Factor V Leiden G1691A (FVL) and Factor II prothrombin G20210A (PGM) mutations are the leading causes of thrombophilia. In this study, we have investigated the prevalence of the FVL G1691A and PGM G20210A single nucleotide polymorphisms (SNPs) among Libyan deep vein thrombosis (DVT) and myocardial infarction (MI) patients. SNP genotyping was performed using high-resolution melt analysis (HRM) and DNA sequencing. Biochemical parameters conducted on 112 males and 93 females showed no significant difference in means between the control group and the deep vein thrombosis and myocardial infarction groups. For Factor V Leiden, 40 samples were genotyped. Of the 40 samples, 6 (15.0%) of them were heterozygous and no one was homozygous. As for Factor II SNP, 59 samples were genotyped and only 2 (3.3%) were heterozygous. All the heterozygous samples showed 100% concordance between the HRM-PCR and DNA sequence analysis. Our study showed, for the first time, that both the FVL and PGM mutations are present among Libyan DVT and MI patients and that the FVL mutation is significantly associated with DVT but not with MI. However, our results do not support the association of PGM G20210A mutation with DVT or MI.

MTHFR Gene Polymorphisms and Cardiovascular Risk Factors, Clinical-Imagistic Features and Outcome in Cerebral Venous Sinus Thrombosis.

Cerebral venous sinus thrombosis (CVST) as a severe neurological emergency, is represented by variable conditions in its clinic presentation, onset, risk factors, neuroimagistic features and outcome. The genetic polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C was associated with CVST. We aimed to characterize the prevalence of MTHFR gene polymorphisms associated with cardiovascular risk factors in the group of patients with CVST. Also, we studied additional causes associated with CVST including local infections, general infections, obstetric causes (pregnancy, puerperium) and head injury. This is a retrospective study including 114 patients which referred to our hospital between February 2012–February 2020. The protocol included demographic (age, sex), clinical, neuroimagistic features, paraclinic (genetic polymorphism of MTHFR, factor V G1691A—Leiden, prothrombin G20210A, PAI-1 675 4G/5G; Homocysteine level, the lipid profile, blood glucose and Glycohemoglobin HbA1c, high- sensitive C- reactive protein- hsCRP) data, as well as treatment and outcome. The mean age was 37.55 years with a female predominance (65.79%). In the first group of patients with inherited thrombophilia (60 cases; 52.63%) we found genetic mutation includes MTHFR C677T (38.59%) and A1298C (14.03%), factor V G1691A- Leiden (15.78%), prothrombin G20210A (2.63%), PAI-1 675 4G/5G (42.98%), and hyperhomocysteinemia (35.08%). At the second group with other etiology of CVST, except thrombophilia, we included 54 patients (47.36%). The most common sites of thrombosis were the superior sagittal sinus (52.63%). Headache was the most common symptom (91.22%) and seizures were the main clinical presentation (54.38%). The MTHFR polymorphism was significantly correlated with higher total cholesterol (TC) (p = 0.023), low- density lipoprotein cholesterol (LDL) (p = 0.008), homocysteine level (tHcy) (p < 0.001). Inside the first group with MTHFR polymorphism we have found a significant difference between the levels of homocysteine at the patients with MTHFR C677T versus MTHFR A1298C polymorphism (p < 0.001). The high-sensitive C-reactive protein (hsCRP) was increased in both groups of patients, but the level was much higher in the second group (p = 0.046). Mortality rate was of 2.63%. Demographic, clinical and neuroimagistic presentation of CVST in our study was similar with other studies on the matter, with a high frequency of thrombophilia causes. MTHFR gene polymorphisms (C677T and A1298C) are increased in prevalence in CVST. PAI-1 675 4G/5G gene mutation seems to be involved in CVST etiology. Plasma C-reactive protein level and hyperhomocysteinemia should be considered as a prognostic factor in CVST.

MTHFR C677T, Prothrombin G20210A, and Factor V Leiden (G1691A) Polymorphism and Beta-Thalassemia Risk: A Meta-Analysis.

BackgroundBeta (β)-thalassemia major patients frequently suffer from many vascular problems. Thrombophilia is a blood disorder that comprises imbalances in the blood coagulating factor due to ecological and hereditary components. Previous evidence shows that thrombosis is the commonest risk in beta-thalassemia patients. Several studies have examined that MTHFR C677T, prothrombin G20210A (PT G20210A), and Factor V Leiden G1691A (FVL G1691A) polymorphism play a crucial role in the development of β-thalassemia major, yet the result was questionable and uncertain. Therefore, in this study, we executed the correlation between these gene polymorphisms with β-thalassemia major patients.MethodsSuitable keywords were used to search related articles in PubMed, Google Scholar, and Web of Science. In this random-effects meta-analysis, we analyzed the odds ratio (OR) for the estimation of risk.ResultsA total of nine research articles with 645 β-thalassemia major patients and 989 healthy controls were incorporated in this meta-analysis. The pooled OR was assessed in MTHFR C677T, PT G20210A, and FVL G1691A polymorphism. This random-effects meta-analysis demonstrated that MTHFR C677T, PT G20210A, and FVL G1691A gene polymorphism did not significantly associate with β-thalassemia major. Moreover, the heterogeneity was significantly found in genotype CC vs CT+TT C677T (I2=61%) and allele C vs T (I2=71%) of MTHFR and genotype GG vs GA (I2=95%), GG vs GA+AA (I2=95%), GA vs GG+AA (I2=95%), and allele G vs A (I2=93%) of FVL G1691A.ConclusionThe results of this meta-analysis show that MTHFR C677T, prothrombin G20210A, and Factor V Leiden (G1691A) gene polymorphism are not a risk factor for β-thalassemia major.

Lack of Association between Factor V Leiden G1691A, Prothrombin G20210A, MTHFC677T Mutations, and Early Recurrent Pregnancy Loss in a Group of Sudanese Women

BACKGROUND: Recurrent pregnancy loss is classically defined as the occurrence of three or more consecutive pregnancy loss. Recurrent pregnancy loss affects from 1-5% of the reproductive age couples. This diagnosis is both emotionally challenging and confusing for most couples, as the definitive diagnosis using conventional evaluations is found in fewer than half of the couples experiencing repeated loss.&#x0D; AIM: The purpose of this study was to define the association between Factor V Leiden G1691A, Prothrombin G20210A, MTHFC677T mutations and recurrent pregnancy loss in a group of Sudanese women.&#x0D; MATERIALS AND METHODS: This a retrospective analytical case control study was carried out at Omdurman Maternal Hospital, Sudan between July 2013 to July 2015. Consent was obtained from the ethical committee of the Faculty Research Board and Hospital of Omdurman Maternity Hospital (Sudan). The study included a hundred pregnant females with a history of recurrent spontaneous abortion as the (case group) and ninety-five healthy reproductive Sudanese women as the (control group). The data was collected with the help of a structured questionnaire and direct interview to collect information. Identification of point mutation in factor V Leiden G1691A, prothrombin G20210A and MTHF C677T gene by polymerase chain reaction was performed. The odds ratio and the 95% confidence interval (95%CI) were calculated for the presence of mutation case group and the control group and analyzed by SPSS program, version 17.0.&#x0D; RESULTS: The frequency of prothrombin G20210A, MTHFC677T, was low overall, except for the Factor V Leiden G1691A. The differences between patients and controls had no statistical significance (P- Value&gt;0.05).&#x0D; CONCLUSION: Our study confirms the low prevalence of inherited thrombophilias in Sudanese populations and it is unlikely that the tested thrombophilias play a role in the pathogenesis of recurrent pregnancy loss in the Sudanse population.Therefore, we conclude that the low prevalence of Factor V Leiden, prothrombin G20210A and MTHFC677T in Sudanese women with RPL and does not play a role in the pathogenesis of recurrent pregnancy loss among our population.