G20210A Gene Research Articles

Investigation of the relationship between MTRR A66G, MTR A2756G gene variations and cell anomalies in early diagnosis and progression of bladder cancer.

The aim of this study is to investigate the relationship between MTRR A66G, MTRA2756G gene variations and cell anomalies in the early diagnosis and progression of bladder cancer. PCR and RFLP methods were used to determine the genotype distributions of MTRR A66G and MTR A2756G gene variations. Peripheral smear preparations prepared from blood samples were fixed with methanol fixative and stained histochemically. Cellular morphological evaluations were made under the light microscope. In our study, AA-GG haplotype was observed significantly more in the patient group than control group (OR: 3.304, 95% CI: 1.023-10.665, p = 0.046). The significant increase was determined in terms of histological damage parameters in the patient group compared to the control group (p < 0.05). For multiple vacuoles damage parameter (mild score), AA genotype of MTR A2756G gene variation was significantly different compared to AA genotype of MTRR A66G gene variation (OR: 0.211, 0.049-0.912, p = 0.037). AA genotype of MTR A2756G gene variation was observed more than AA homozygous genotype of MTR A66G gene variation for giant platelets with different sizes damage parameter (mild score) (OR: 0.062, 0.017-0.228, p < 0.001). In conclusion, in Thrace population, AA genotype of the MTR A2756G gene variation was significantly higher than the AA homozygous genotype of the MTR A66G gene variation as a genetic risk factor for the multiple vacuoles damage parameter. In addition, AA genotype of MTR A2756G gene variation was determined as a genetic risk factor for giant platelets with different sizes damage parameter.

Thrombophilic mutations and risk of vascular complications in sickle cell disease

IntroductionSickle cell disease (SCD) is an inherited hemoglobinopathy that is characterized by hemolysis and hypercoagulability. The coinheritance of genetic variants causing thrombophilia may aggravate the hypercoagulable state in SCD patients. The identification of SCD patients with the risk factors for developing thrombosis may play an important role in the prevention and management of vaso-occlusive crises (VOCs) and vascular complications in these patients. The objective of the current case control study was to determine the relationship between thrombophilic variants, methylenetetrahydrofolate reductase (MTHFR) C677T, Factor V Leiden (FVLG1691A), prothrombin gene (PRT) G20210A variants and susceptibility to VOCs and vascular complications in Egyptian SCD patients. Patients and methodsEighty two patients (53 SS, 29 S/β thalassemia) and 70 healthy individuals were genotyped for these thrombophilic variants using PCR-RFLP. Sanger sequencing and real time PCR-based SNP genotyping assay were done for positive cases. ResultsMTHFR C677T was found in 40.2% of cases in heterozygous state (43.4% of SS, 34.5% of S/β thalassemia) with a highly significant difference in the prevalence between cases and healthy subjects (P = 0.001). Heterozygous FVLG1691A mutation was found in 13.4% of cases (15.1% of SS, 10.3% of S/β thalassemia). Seven cases carried both FVLG1691A and MTHFR C677T variants. There was a statistical significant difference between the frequency of acute painful crises and the heterozygosity for MTHFR C677T and FVLG1691A variants (P = 0.003). The heterozygote state of PRT G20210A mutation was present in one SS patient. ConclusionOur data suggested that the MTHFR C677T and FVLG1691A variants have a high impact as risk factors for VOCs in SCD.

A unique case of Lemierre&amp;apos;s Syndrome and cerebral vein thrombosis in a carrier of prothrombin gene G20210A mutation

Introduction: We describe here a case of a woman admitted to our Internal Medicine Unit for multifocal pneumonia. During the stay, she presented a few neurological symptoms: headache, nausea, emesis, photophobia, and gait disturbance. Methodology: Chest computed tomography (CT) detected multiple areas interpreted as septic emboli. Moreover, a left internal jugular thrombosis (LIJT) was incidentally reported. A CT-angiography showed the LIJT extension to cerebral sinuses. Ear, nose, and throat consultation revealed a left medium otitis. Anticoagulation with Fondaparinux was associated to antibiotic therapy with improvement in neurological symptoms that totally remitted over the next 2 weeks. Results: These findings confirmed the diagnosis of a Lemierre&amp;apos;s Syndrome with thrombosis extension to cerebral sinuses. The genetic thrombophilic panel showed a heterozygosis for prothrombin gene G20210A mutation and the patient was discharged with Rivaroxaban for home continuation of anticoagulant therapy for at least 6 months. Conclusion: The prevalence of inherited thrombophilias in Lemierre&amp;apos;s Syndrome is unknown and to our knowledge, this article is the first to identify a prothrombin gene G20210A mutation in a patient with Lemierre&amp;apos;s Syndrome with thrombosis extension into the cerebral venous system. Exploring patients with Lemierre&amp;apos;s Syndrome for underlying thrombophilia could clarify whether this promotes retrograde jugular vein thrombosis extension.

MTHFR C677T and MTR A2756G Gene Polymorphism in Neural Tube Defect Patients and Its Association with Red Blood Cell Folate Level in Eastern Indian Population.

Single-nucleotide polymorphism (SNP) is a single-nucleotide change in a deoxyribose nucleic acid (DNA) sequence that occurs in >1% of population. Methylene tetra hydro folate reductase (MTHFR) C677T (rs1801133) and methionine synthase enzyme (MTR) A2756G (rs1805087) are two such SNPs occurring in coding sequence of the respective genes, which are frequently seen with neural tube defects (NTDs). MTHFR and MTR genes are involved in folate metabolism. The folate level in the course of pregnancy is treated as vital in the etiopathogenesis of NTDs. This study aims to explore the association of SNPs of both genes and red blood cell (RBC) folate levels in the predisposition to NTDs. The purpose of this investigation was to determine the relationship of NTDs with polymorphisms in MTHFR and MTR genotype and to estimate and compare the RBC folate levels in NTD patients and controls. A total of 397 individuals were enrolled (163 patients and 234 controls) for this observational study. Genotyping to find out MTHFR C677T and MTR A2756G was performed by polymerase chain reaction-restriction fragment length polymorphism technique from DNA extracted from the subject's blood. RBC folate level was estimated by chemiluminescence immunoassay method with the same blood sample. The total RBC folate levels were significantly less among cases compared to controls (P = 0.020). A significant difference for RBC folate was observed between case and control groups of various genotypes of MTHFR C677T, except heterozygote CT (P = 0.459). Among MTR A2756G, genotypes with only homozygous AA have significant difference (P = 0.003) for RBC folate levels. Among different types of NTDs, there were no significant differences for RBC folate levels. Among MTHFR C677T, T allele possessed 1.9 times risk compared to C allele for the occurrence of NTDs. In MTR A2756G polymorphism, the odds of developing NTDs were 1.6 times in heterozygous AG compared to homozygous AA. Similarly, the risk for NTDs was three times higher in subjects with both heterozygous AG and CT genotypes compared to wild-type homozygous AA and CC genotypes. The total RBC folate levels were significantly less among cases compared to controls, and the genotypes had no such effect in decrease in RBC folate levels. The presence of mutant allele in homozygous or heterozygous condition for both SNPs had increased risk associated with NTDs.

From the Editor’s Desk...

From the Editor’s Desk...

Risk Factors of Venous Thromboembolism in Sudanese Pregnant Women.

Venous thromboembolism (VTE) is one of the major causes of pregnancy-related mortality and morbidity. This study aimed to determine the frequency of factor V Leiden (FVL) and prothrombin G20210A polymorphisms and measure the plasma levels of protein C (PC), protein S (PS) and antithrombin (AT) in pregnant women with VTE and healthy pregnant women. This prospective case-control study determined the frequencies of FVL G1691A and prothrombin G20210A polymorphisms and measured the plasma levels of PC, PS and AT in 198 pregnant women with VTE and 198 healthy pregnant women. Allele-specific polymerase chain reaction (ASPCR) was used to detect the FVL G1691A polymorphisms and prothrombin G20210A gene mutations. The FVL G1691A polymorphism and prothrombin G20210A gene mutations were detected only in pregnant women with VTE, with frequencies of 4.0 and 0.5%, respectively. The highest frequency of FVL G1691A polymorphism was observed in patients with deep vein thrombosis (DVT) and positively associated with contraceptive use and termination. Pregnant women with VTE had significantly lower levels of PC, PS and AT than those of controls. In conclusion, among the VTE cases, FVL G1691A polymorphism and PC, PS and AT deficiencies were the most common findings in patients presenting with DVT. Antithrombin deficiency was more common than PC and PS deficiencies. Contraceptive use, high body mass index (BMI) and termination correlated strongly with FVL G1691A polymorphism and PC and PS deficiencies in patients with VTE.

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.

The involvement of the factor V G1691A gene on recurrent ischemic stroke in young adults

Although the association between traditional risk factors and ischemic stroke (IS) recurrence has been widely studied, the involvement of inherited thrombophilia such as the factor V G1691A gene (FV) in stroke recurrence has not been clearly defined. This study aims to determine the involvement of the FV in recurrent ischemic stroke in young Tunisians.

Multicenter study on recent portal venous system thrombosis associated with cytomegalovirus disease

Recent non-malignant non-cirrhotic portal venous system thrombosis (PVT) is a rare condition. Among risk factors for PVT, cytomegalovirus (CMV) disease is usually listed based on a small number of reported cases. The aim of this study was to determine the characteristics and outcomes of PVT associated with CMV disease. We conducted a French multicenter retrospective study comparing patients with recent PVT and CMV disease ("CMV positive"; n= 23) to patients with recent PVT for whom CMV testing was negative ("CMV negative"; n= 53) or unavailable ("CMV unknown"; n= 297). Compared to patients from the "CMV negative" and "CMV unknown" groups, patients from the "CMV positive" group were younger, more frequently had fever, and had higher heart rate, lymphocyte count and serum ALT levels (p ≤0.01 for all). The prevalence of immunosuppression did not differ between the 3 groups (4%, 4% and 6%, respectively). Extension of PVT was similar between the 3 groups. Thirteen out of 23 "CMV positive" patients had another risk factor for thrombosis. Besides CMV disease, the number of risk factors for thrombosis was similar between the 3 groups. Heterozygosity for the prothrombin G20210A gene variant was more frequent in "CMV positive" patients (22%) than in the "CMV negative" (4%, p= 0.01) and "CMV unknown" (8%, p= 0.03) groups. Recanalization rate was not influenced by CMV status. In patients with recent PVT, features of mononucleosis syndrome should raise suspicion of CMV disease. CMV disease does not influence thrombosis extension nor recanalization. More than half of "CMV positive" patients have another risk factor for thrombosis, with a particular link to the prothrombin G20210A gene variant. Patients with cytomegalovirus (CMV)-associated portal venous system thrombosis have similar thrombosis extension and evolution as patients without CMV disease. However, patients with CMV-associated portal venous system thrombosis more frequently have the prothrombin G20210A gene variant, suggesting that these entities act synergistically to promote thrombosis.

Factor V H1299r (Hr2) Heterozygosity: A Risk Factor For Recurrent Implantation Failure Particularly In Non-Carriers For Factor V Leiden Mutation-A Case-Control Study

Objective: The association between recurrent implantation failure and thrombophilia is still controversial depending on the published reports with conflicting results. In this study, we aimed to assess the clinical relevance of screening women with recurrent implantation failure for some thrombophilic variants including factor V H1299R (FV HR2) haplotype. Study Design: A total of 279 women were recruited in this case-control study. 229 women with a history of recurrent implantation failure and 50 fertile control with no history of pregnancy losses were screened for eight specific gene mutations, regarding factor V G1691A gene (FV Leiden), FV HR2, factor II prothrombin G20210A, factor XIII V34L, PAI-1 4G/5G, MTHFR C677T, MTHFR A1298C and A3 haplotype of the endothelial cell protein C receptor gene. Results: Recurrent implantation failure group displayed a significantly higher prevalence of FV HR2 heterozygosity than fertile controls while the frequency of FV Leiden mutation was comparable between groups (p=0.011; p=0.619). Additionally, the difference in the prevalence of other specific or total gene mutations among women with recurrent implantation failure was also insignificant. Discussion: The primer outcome of this study was the co-existence of the higher prevalence of FV HR2 haplotype and the insignificant percentage of FV Leiden mutation in women with recurrent implantation failure. Thus, we emphasize that the HR2 haplotype may be associated with recurrent implantation failure particularly in non-carriers for FV Leiden mutation. In the necessity of screening for thrombophilia in recurrent implantation failure, HR2 haplotype should be involved in the searched gene panel particularly in the absence of FV Leiden mutation. Further large-scale prospective studies are needed to investigate whether screening or treatment for HR2 haplotype has any detrimental impact on implantation success in cases of recurrent implantation failure.

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.

Factor V Leiden G1691A and Prothrombin Gene G20210A Mutations on Pregnancy Outcome.

Factor V Leiden (FVL) G1619A mutation and prothrombin gene (PTG) G20210A are the most common inherited thrombophilias. They have been associated with various obstetric complications such as venous thromboembolism, recurrent pregnancy loss, preeclampsia, abruptio placentae, and small for gestational age fetus. The prevalence of these two mutations is 3-15% in Caucasians and is assumed to be far less common in other ethnic populations. However, there have been several controversies regarding advising routine screening of these thrombophilias because of a widely variable strength of association between different ethnic groups, as well as contradictory conclusions by different studies in regards to the association. In this study, the literature was analyzed thoroughly for the effect of FVL G1619A and PTG G20210A mutations on various obstetric outcomes. A review of multiple case-control and prospective studies suggests that despite the availability of robust data on this subject the results remain inconclusive and insubstantial. Further superior quality research, preferably prospective studies, is warranted to conclusively establish this relationship and to enable practitioners to follow a definitive protocol in the screening of various populations for these mutations to achieve an improved pregnancy outcome.

Associations of Tumor Necrosis Factor–α G-308A (rs1800629) Gene Polymorphisms with Major Depressive Disorder

Pro-inflammatory cytokine polymorphisms like Tumor Necrosis Factor- (TNF), has been found associated to severe depressive disorder (MDD). The Pro-inflammatory cytokines tumor necrosis factor (TNF-α) G-308A (rs1800629) have been discovered to have an important role in the pathophysiology of depressive disorders and the mechanism of antidepressant treatment. The present study aims to study TNF-α gene polymorphisms in Major depressive disorder using allele specific PCR. The results show that family history are non- significant different between patients and control group (0.6346) and also there was non- significant different in BMI (0.3417), The genotyping data show tow alleles and three genotyping (AG, GG, AA) the statically analysis show non-significant differences between patients and controls groups (0.095, 0.800) for GG, AA and GA respectively with more frequent of GA in patients than control group, the G allele was less frequent in patient than control while A allele was more frequent in patients than control group in significant differences (0.0001). It can be concluded that TNF genotyping didn’t impact in the Major depressive disorder but the allele distribution may have potential role in MDD patients.

Age and ABO Blood Group Are Significant Predictors of Thrombosis in Children with Acute Lymphoblastic Leukemia (ALL): Results from Dana-Farber Cancer Institute (DFCI) ALL Consortium Trial 05-001

BackgroundThromboembolism (TE) is a serious complication in pediatric patients with ALL associated with significant morbidity, mortality and therapy alterations. Thromboprophylaxis, though effective in preventing TE in patients at high risk for TE, is associated with increased risk of bleeding. Hence it is important to identify the population at the highest risk for TE for whom preventive strategies may be warranted. However, predictors of TE in pediatric patients with ALL remain uncertain and the role of inherited thrombophilia is ill defined. Adult studies of non-cancer patients and our prior smaller pilot study of pediatric ALL patients showed higher rates of TE with non-O blood types.AimTo identify variables at the time of ALL diagnosis that are associated with increased risk of TE in children and adolescents treated on DFCI ALL 05-001 trial.Design/MethodsEligible and consenting patients (1 to ≤18 yrs. of age) with newly diagnosedALL were enrolled on the DFCI 05-001 trial between 2005-2011 at 11 participating institutions in the USA and Canada. Risk categorization and protocol therapy have previously been described (Lancet Oncol 2015;16:1677-90). Treatment included one dose of pegaspargase (2500 IU/m2) during remission induction and 30 consecutive weeks of L-asparaginase during post-induction therapy (either pegaspargase 2500 IU/m2 every 2-weeks or native E.coli L-asparaginase 25000 IU/m2 weekly). Baseline clinical and laboratory data as well as all TE events requiring intervention (Grade 2 or higher) were prospectively collected. Genomic DNA was isolated from peripheral blood or bone marrow obtained at the time of complete remission in participants who consented for the collection of research samples. Single nucleotide polymorphisms (SNP) were detected using PCR-based allelic discrimination assays for prothrombin (PT)gene G20210A (rs1799963) and Factor V G1691A (rs6025) (Factor V Leiden, FVL) (Applied Biosystems, Carlsbad CA). The cumulative incidence of TE was estimated with induction failure, relapse and death considered as competing events. Effect of clinical [age, gender, body mass index (BMI) ALL immunophenotype, risk-group] and laboratory variables [presenting leukocyte count, blood group, SNPs for PT and FVL] at ALL diagnosis on the cumulative incidence of TE was evaluated in univariate and multivariable competing risk regression models. The impact of TE on ALL outcome (event free and overall survival) was further explored using a time-varying covariate in Cox regression modelling.ResultsOf 794 enrolled patients [median age 4.97 (range 1.04 -17.96) yrs.; males 441], 100 developed TE; the 25-month cumulative incidence was 13.0% (95%CI 10.7,15.5). Twenty-one patients had 21 events during induction (3 with CNS TE) and 79 patients had 88 events post-induction (16 CNS TE). Table 1 provides the cumulative incidence of the time to first event of TE by patient characteristics and is compared using Gray test. Sex, BMI and thrombophilia SNPs had no detectable impact on the incidence of TE. There was no difference in incidence of TE by asparaginase type (data not shown). In the final competing risk multivariable regression model older age group and non-O blood group were each significantly associated with TE (Table 2). Figure 1 depicts the effect of blood group type on the incidence of TE within each age group; the cumulative incidence of TE was significantly higher for non-O blood group only for patients <5 years of age (p=0.01). There was no difference in the event free or overall survival between patients with or without TE.ConclusionOlder age and non-O blood group are significant predictors of TE during ALL therapy. The effect of non-O blood group is more pronounced in younger age patients. Polymorphisms of FVL and PT gene had no impact on the risk of TE. We recommend further evaluation of these risk factors and recommend thromboprophylaxis for pediatric patients with ALL over 10 years of age (and especially those 15 years or older) receiving asparaginase-intensive regimens, and consideration of thromboprophylaxis in younger patients with non-O blood group. [Display omitted] DisclosuresNeuberg:Synta Pharmaceuticals: Other: Stock shares.

MO322VENOUS THROMBOEMBOLISM AND NEPHROTIC SYDROME: A FAMOUS BUT STILL SURPRISING COUPLE

Abstract Background Venous thromboembolism (VTE) is a multifactorial disorder, accounting for high morbidity and mortality rates, due to a complex interplay of several variables classifiable as inherited (mutated Leiden V factor, prothrombin, protein C, protein S and antithrombin) and acquired (lupus anticoagulants, pregnancy, major surgery procedures, cancer and inflammatory diseases) risk factors. The association of VTE with the nephrotic syndrome, particularly deep vein and renal vein thrombosis (DVT and RVT, respectively) is tightly established. This risk is particularly high in patients with idiopathic membranous nephropathy. In fact, thromboembolic events occur with a frequency between &amp;lt;10% and 45% in this disease. The reason(s) underlying the hypercoagulable status in nephrotic patients are not clearly understood. Multiple hemostatic abnormalities have been described, including decreased levels of antithrombin and plasminogen (due to urinary losses), increased platelet activation, reduced plasminogen activation, overproduction of fibrinogen and factors V and VIII as a compensatory response to hypoalbuminemia. The risk of thrombosis seems to be related to the severity and duration of the nephrotic status and seems to be particularly increased with serum albumin concentrations ≤2.0 g/dl (20 g/L). Case report We report the case of a 28 year-old male with nephrotic syndrome due to membranous nephropathy positive for serum anti-phospholipase-A2 receptor antibody. The patient was asymptomatic for VTE, but abdominal ultrasound showed endoluminal obstruction of both renal veins. Abdominal Computer Tomography confirmed the extensive bilateral renal vein thrombosis and also revealed an extension of the thrombosis to the inferior cava vein and the left common iliac vein. He was treated with low-molecular weight heparin for six months. According to our internal protocol, a complete Thrombophilia Molecular Study was performed and showed a normal Leiden V factor, but a rare homozygous mutation of the G20210A gene encoding for prothrombin. The prevalence of this is less than 5% in the general population, but is highly variable with ethnicity. The G20210A mutation confers a mildly increased thrombotic risk that is amplified by the presence of other risk factors, such as nephrotic syndrome. Conclusions In our case report, the association of a nephrotic syndrome secondary to a primitive membranous glomerulonephritis and the mutation in homozygous of the G20210A prothrombin, a rare mutation associated with a high thrombotic risk, led to a severe VTE in an still asymptomatic 28-year-old patient. Based on this experience, we would highlight the importance of the genetic screening for polymorphisms associated with inherited thrombophilia in nephrotic patients complicated with VTE.

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.

Correlation between the Polymorphism of Coagulation-Related Genes and Lower Extremity Deep Venous Thrombosis.

Objective To investigate the correlation between the polymorphism of 4 coagulation-related genes, rs1799963 （coagulation factor V gene Leiden）, rs6025 （prothrombin gene G20210A）, rs1042579 （thrombomodulin protein gene c.1418C>T） and rs1801131 （methylenetetrahydroflate reductase gene） and lower extremity deep venous thrombosis （LEDVT）. Methods The 4 genotypes mentioned above of 150 LEDVT patients and 153 healthy controls were detected by the kompetitive allele specific polymerase chain reaction （KASP）, then related blood biochemical indicators were collected, binary Logistic regression was established to screen the independent risk factors of LEDVT, and the correlation between polymorphism of 4 coagulation-related genes and LEDVT and its indicators under different genetic modes after adjusting confounding factors were analyzed. Results Five variables, D-dimer, fibrinogen degradation product, homocysteine, sex and age might be the risk factors of LEDVT. These variables were put into 4 genetic inheritance models, and adjusted in binary Logistic regression. The results suggested that the mutations of rs1042579 were correlated with LEDVT under dominant inheritance mode. Conclusion The gene polymorphism of rs1799963, rs6025 and rs1801131 has no significant correlation with the formation of LEDVT. The gene polymorphism of rs1042579 plays a role under dominant inheritance mode, and might be an independent risk factor for formation of LEDVT.

THE STUDY OF CORRELATION BETWEEN LEIDEN V FACTOR AND METHYLEN TETRAHYDROFOLATE REDUCTASE ENZYME GENE MUTATIONS IN PRIMIGRAVIDA WITH MISSED ABORTION IN LATE FIRST TRIMESTER

Pregnancy is a hypercoagulable state secondary to an increase in coagulation factors, a reduction in naturally occurring anticoagulants, and impairment of fibrinolysis. Pregnancy losses were divided into preclinical, first trimester clinical, and second trimester. A meaningfully increased rate of preclinical pregnancy failure in Leiden mutation carriers was found than in no activated protein C deficiency patients. Another cause of miscarriages is inherited thrombophilia following damage to the maternal factor V gene G1691A (Leiden mutation) and prothrombin gene (G20210A mutation). These alterations are well studied and the test is part of the routine diagnostics of recurrent mis-carriages. In the case of factor V, both the Leiden mutation G1691A and the T1328C mutation appear to be important in the pathogenesis of RM, mainly in cases observed before the 7th week of gestation. The most common causes of inherited thrombophilia are polymorphisms in genes encoding factor V, prothrombin (factor II), factor VII, MTHFR, and plasminogen activator inhibitor, while protein C, protein S and ant thrombin deficiency is less common. The finding of a link between FVL carrier state and early RPL would have significant implications for clinical practice, as it would provide a scientific rationale for screening for FVL mutation and targeted thromboprophylaxisin affected women.

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.

Inherited and acquired thrombophilia in women of Indian ethnicity with recurrent pregnancy loss: An observational study from North India.

The spectrum of thrombophilia in women with recurrent pregnancy loss (RPL) is different in Indian ethnicity as reported by few studies. We aimed to study the prevalence of thrombophilia in RPL patients referred to hematology department of a tertiary centre. This is an observational study of 112 RPL patients with no apparent cause after extensive workup for non-hematological causes. The investigations performed were routine coagulogram, APLA workup, plasma homocysteine, MTHFRC677T polymorphisms, Protein C, free Protein S, Anti-thrombin III levels, test for Activated Protein C resistance (APC-R) ,Factor V Leiden and Prothrombin gene G20210A mutation. Of 112 patients, at least one thrombophilia was identified in 70.5% and combined thrombophilia in 12.5% patients. Hyperhomocysteinemia (30.4%) and APLA (25.9%) were the commonest thrombophilia whereas anticoagulant defects were seen in 12.5% of the population. Protein C deficiency (5.35%) was the commonest anticoagulant defect followed by APCR (3.6%). Mutational analysis revealed MTHFRC677T polymorphism in 20.5% whereas Factor V Leiden heterozygous in 1.8% patients. None of the patients had homozygous Factor V Leiden or Prothrombin gene G20210A mutation. Hyperhomocysteinemia, MTHFRC677T and Protein C deficiency were more associated with early pregnancy losses whereas Protein S deficiency, Factor V Leiden and APLA caused both early and late losses. Patients with greater number of losses were positive for homozygous MTHFRC677T, factor V Leiden and APLA. The approach to investigating Indian women with RPL should be based on the prevalence of thrombophilia which is unique to Indian ethnicity.