Prothrombin G20210A Polymorphism Research Articles

Investigating the Matrix of Factor V Leiden (G1691A), Factor II Prothrombin (G2021A), MTHFR C677T and A1298G Polymorphisms in Greek Population: A Preliminary Study

Background: Thrombophilia, characterized by an increased risk of thrombosis, can result from genetic polymorphisms in clotting factors. This study aims to investigate the prevalence of factor V Leiden (G1691A), factor II prothrombin (G20210A), and MTHFR (C677T and A1298C) polymorphisms in a Greek population, evaluating not only their association with thrombophilia, but also broader health implications. Methods: We conducted a cross-sectional study involving one hundred apparently healthy adults from Thessaloniki, Greece. After obtaining informed consent, DNA was isolated and analyzed using real-time PCR to detect the frequencies of the aforementioned polymorphisms. Results: The genetic distribution of the examined polymorphisms aligns closely with that observed in Northern Europe. Factor V Leiden (FVL) and prothrombin G20210A mutations were predominantly wild types, with a small percentage showing heterozygous mutations. The MTHFR C677T and A1298C polymorphisms showed a higher variation in allele frequency. Certain lifestyle factors such as smoking and high body mass index were significantly associated with the occurrence of combined MTHFR genotypes, suggesting an interaction between genetic and environmental risk factors. Family cancer and cardiovascular history was significantly associated with combined FVL and prothrombin G20210A and MTHFR polymorphism heterozygous carriers. Conclusions: Our findings indicate that these genetic polymorphisms are not only pivotal in understanding thrombophilia but also have broader implications for cardiovascular disease and cancer. This study highlights the need for further research into the combined effects of genetic and epigenetic factors on health, which could lead to improved screening and personalized preventive healthcare strategies.

Thrombosis risk in single- and double-heterozygous carriers of factor V Leiden and prothrombin G20210A in FinnGen and the UK Biobank

AbstractThe factor V Leiden (FVL; rs6025) and prothrombin G20210A (PTGM; rs1799963) polymorphisms are 2 of the most well-studied genetic risk factors for venous thromboembolism (VTE). However, double heterozygosity (DH) for FVL and PTGM remains poorly understood, with previous studies showing marked disagreement regarding thrombosis risk conferred by the DH genotype. Using multidimensional data from the UK Biobank (UKB) and FinnGen biorepositories, we evaluated the clinical impact of DH carrier status across 937 939 individuals. We found that 662 participants (0.07%) were DH carriers. After adjustment for age, sex, and ancestry, DH individuals experienced a markedly elevated risk of VTE compared with wild-type individuals (odds ratio [OR] = 5.24; 95% confidence interval [CI], 4.01-6.84; P = 4.8 × 10−34), which approximated the risk conferred by FVL homozygosity. A secondary analysis restricted to UKB participants (N = 445 144) found that effect size estimates for the DH genotype remained largely unchanged (OR = 4.53; 95% CI, 3.42-5.90; P < 1 × 10−16) after adjustment for commonly cited VTE risk factors, such as body mass index, blood type, and markers of inflammation. In contrast, the DH genotype was not associated with a significantly higher risk of any arterial thrombosis phenotype, including stroke, myocardial infarction, and peripheral artery disease. In summary, we leveraged population-scale genomic data sets to conduct, to our knowledge, the largest study to date on the DH genotype and were able to establish far more precise effect size estimates than previously possible. Our findings indicate that the DH genotype may occur as frequently as FVL homozygosity and may confer a similarly increased risk of VTE.

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.

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.

Association of increased C-Reactive Protein and hypocomplementemia with risk factors for thrombosis in women who have susceptibility for poor gestational outcome; importance of preconceptional counseling.

This study aimed to investigate the association of increased C-Reactive Protein (CRP) and hypocomplementemia with risk factors for thrombosis such as Factor V Leiden (FVLP) and Prothrombin G20210A polymorphisms (PP), increased Activated Protein C Resistance (APCR) and decreased anti-thrombin III (ATIII) activity in women who have metabolic (MTHFR polymorphisms) and immunological risk factors (autoimmune antibody positivity, autoimmune disorders, and chronic inflammatory diseases). All patients (n= 197) were evaluated in terms of risk factors for thrombosis including FVLP, PP, increased APCR, and decreased ATIII activity as well as CRP and complement (C) 3 and C4 levels within a framework of preconceptional care program. Patients with high CRP levels together with hypocomplementemia were included to the study group (n= 13), while women with normal levels of CRP, C3, and C4 were accepted as controls (n= 184). Decreased ATIII activity was found to be statistically more frequent in the study group compared to controls (p= 0.036). There were no significant differences between the study and control groups in terms of the presence of FVLP, PP and increased APCR (p= 0.386, p= 0.462, p= 0.625, respectively). Decreased ATIII activity should be the concern of preconceptional and antenatal care programs in risky patients with increased CRP levels and hypocomplementemia in order to prevent placental inflammation related gestational complications.

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.

PlA2 Polymorphism of Platelet Glycoprotein IIb/IIIa and C677T Polymorphism of Methylenetetrahydrofolate Reductase (MTHFR), but Not Factor V Leiden and Prothrombin G20210A Polymorphisms, Are Associated with More Severe Forms of Legg-Calvé-Perthes Disease.

The possible association of common polymorphic variants related to thrombophilia (the rs6025(A) allele encoding the Leiden mutation, rs1799963(A), i.e., the G20210A mutation of the prothrombin F2 gene, the rs1801133(T) variant of the methylenetetrahydrofolate reductase (MTHFR) gene that encodes an enzyme involved in folate metabolism, and rs5918(C), i.e., the ‘A2’ allele of the platelet-specific alloantigen system that increases platelet aggregation induced by agonists), with the risk of Legg–Calvé–Perthes disease (LCPD) and the degree of hip involvement (Catterall stages I to IV) was analyzed in a cohort study, including 41 children of ages 2 to 10.9 (mean 5.4, SD 2.2), on the basis of clinical and radiological criteria of LCPD. In 10 of the cases, hip involvement was bilateral; thus, a total of 51 hips were followed-up for a mean of 75.5 months. The distribution of genotypes among patients and 118 controls showed no significant differences, with a slightly increased risk for LCPD in rs6025(A) carriers (OR: 2.9, CI: 0.2–47.8). Regarding the severity of LCPD based on Catterall classification, the rs1801133(T) variant of the MTHFR gene and the rs5918(C) variant of the platelet glycoprotein IIb/IIIa were associated with more severe forms of Perthes disease (Catterall III–IV) (p < 0.05). The four children homozygous for mutated MTHFR had a severe form of the disease (Stage IV of Catterall) and a higher risk of non-favorable outcome (Stulberg IV–V).

Basophil Blood Cell Count Is Associated With Enhanced Factor II Plasma Coagulant Activity and Increased Risk of Mortality in Patients With Stable Coronary Artery Disease: Not Only Neutrophils as Prognostic Marker in Ischemic Heart Disease.

BackgroundWhite blood cell count, which is inexpensive and widely available in clinical practice, has been proposed to provide prognostic information in coronary artery disease (CAD). Elevated levels of white blood cell subtypes may play different roles in atherothrombosis and predict cardiovascular outcomes.Methods and ResultsThe association between white blood cell counts and mortality was evaluated in 823 subjects with angiographically demonstrated and clinically stable CAD in an observational–longitudinal study. The correlation among white blood cell counts and factor II plasma coagulant activity was analyzed in 750 subjects (554 CAD and 196 CAD‐free) not taking anticoagulant drugs. Subjects with overt leukocytosis or leukopenia were excluded. In the longitudinal study after a median follow‐up of 61 months, 160 (19.4%) subjects died, 107 (13.0%) of whom from cardiovascular causes. High levels of neutrophils, monocytes, eosinophils, and basophils were associated with an increased mortality rate. In multiadjusted Cox regression models, only neutrophils and basophils remained predictors of total and cardiovascular mortality. The associations remained significant after adjustment for traditional cardiovascular risk factors and by including D‐dimer and the chemokine CXCL12 in the regression models. Neutrophils and basophils were also significant predictors of factor II plasma coagulant activity variability after adjustment for blood cell counts, age, sex, inflammatory markers, CAD diagnosis, and prothrombin G20210A polymorphism. Factor II plasma coagulant activity was similarly increased in subjects with high neutrophil and basophil counts and in carriers of the prothrombin 20210A allele.ConclusionsBoth high neutrophil and basophil blood counts may predict mortality in patients with clinically stable CAD and are associated with enhanced factor II plasma coagulant activity, thereby suggesting underlying prothrombotic mechanisms.

Роль предрасполагающих факторов в развитии тромбоза глубоких вен у пациентов пожилого и старческого возраста

Введение. Тромбоз глубоких вен (ТГВ) является жизнеугрожающим заболеванием и осложнением, имеющим большое количество этиологических факторов. В современной литературе основным предрасполагающим фактором развития ТГВ в пожилом и старческом возрасте принято считать онкологические заболевания. Цель исследования: оптимизировать скрининговую диагностику и тактику антикоагулянтной терапии у пациентов пожилого и старческого возраста с ТГВ в зависимости от этиологического фактора. Материалы и методы. В рамках исследования проводили лечение 40 больных c ТГВ из них 29 пациентов находились на амбулаторном лечении, 11 на стационарном. Среди них было 18 (45) мужчин и 22 (55) женщины в возрасте от 61 года до 87 лет, средний возраст составил 72 года. Диагноз ТГВ устанавливали на основании клинического обследования и данных ультразвукового дуплексного сканирования (УЗДС) вен нижних конечностей. Амбулаторно обследовались и получали лечение пациенты с низким риском развития тромбоэмболии легочной артерии по шкале Geneva. Все пациенты сдавали анализы крови на наличие наследственных тромбофилий. Наблюдение осуществляли в течение 1 года, что включало визиты в клинику и телефонные звонки, а также регулярные УЗДС нижних конечностей и лабораторный контроль пациента через 3, 14 дней, 1, 3, 6 мес и 1 год. Результаты. У 26 (65) человек тромботический процесс локализовался в подвздошно-бедренном сегменте, изолированный дистальный тромбоз обнаружен у 8 (20) пациентов. Новообразования найдены у 16 (40) обследованных, причем в органах малого таза в 33 случаев. По классификации ТNM (tumor, nodus, metastasis) выявленные онкологические патологии были представлены IIII стадиями. У 6 (9) пациентов обнаружена мутация V фактора (Лейденская мутация) свертывания крови (у 5 гетерозиготная, у 1 гомозиготная), 3 (3) пациента имели мутацию гена протромбина (у всех гетерозиготная). Заключение. Генетические тромбофилии очень скромный предиктор развития ТГВ у пациентов пожилого и старческого возраста. Онкологическая патология является более сильным драйвером тромбоза глубоких вен, чем генетическая предрасположенность. Introduction. Deep vein thrombosis (DVT) is a life-threatening disease and complication, and has a large number of etiological factors. In modern literature cancer is considered to be the main predisposing factor for DVT development in elderly and senile age. Aim: to optimize the screening diagnostics and tactics of anticoagulant therapy in elderly and senile patients with DVT depending from etiological factor. Materials and methods. We treated 40 patients with DVT 29 of them were outpatient and 11 inpatient. Among them were 18 (45) men and 22 (55) women aged 6187 years, the average age was 72 years. DVT was diagnosed on the basis of clinical examination and ultrasound duplex scanning (USDS) of the veins of lower extremities. Patients with a low risk of pulmonary embolism according to the Geneva scale were examined and received treatment on an outpatient basis. All patients were examined for hereditary thrombophilia. The observation was carried out for 1 year: visits to the clinic and phone calls, as well as regular USDS of the lower extremities and laboratory monitoring after 3, 14 days, 1, 3, 6 months and 1 year. Results. In 26 (65) patients the thrombotic process was localized in the ileo-femoral segment isolated distal thrombosis was found in 8 (20) patients. Neoplasms were found in 16 (40) patients, and in pelvic organs in 33 of cases. According to the TNM classification (tumor, nodus, metastasis), the identified oncological pathologies were represented by stages IIII. In 6 (9) patients factor V mutation (Leiden mutation) of blood coagulation was detected (in 5 heterozygous, in 1 homozygous), 3 (3) patients had a prothrombin gene mutation (all heterozygous). Conclusion. Genetic thrombophilia is a very modest predictor of DVT development in elderly and senile patients. Oncological pathology is a stronger driver of DVT than a genetic predisposition.

Common Variations in Prothrombotic Genes and Susceptibility to Ischemic Stroke in Young Patients: A Case-Control Study in Southeast Iran.

Background and Objective: Evidence indicates that genetic factors may be involved in the risk of ischemic stroke (IS). The aim of this study was to assess the effect of genetic polymorphisms located in exons or untranslated regions of MTHFR as well as FV genes on ischemic stroke. Materials and Methods: In this case-control study, 106 patients with IS and 157 healthy volunteers (age <50 years) were genotyped for MTHFR C677T, A1298C, C2572A and C4869G, FVL, and prothrombin G20210A polymorphisms. Results: The MTHFR 677CT genotype was more frequent in patients and increased risk of IS with Odds Ratio = 1.9. The MTHFR A1298C and C2572A polymorphisms were not associated with IS in dominant and recessive models. Our findings showed a significant decrease in the MTHFR 4869CG genotype in IS patients, and this variant was associated with a decreased risk of IS in the dominant model. The CAAT haplotype was associated with increased risk, and the GAAC haplotype was associated with decreased risk of IS compared to other haplotypes. There was no relation between FVL G1691A polymorphism and IS risk. Conclusions: The present study showed that the MTHFR 677CT genotype was more frequent and the MTHFR 4869CG genotype was less frequent in young IS patients.

Factor-V Leiden G1691A and prothrombin G20210A polymorphisms in Sudanese women with preeclampsia, a case -control study

BackgroundPreeclampsia can lead to adverse maternal and perinatal outcomes. There are few studies on the association of preeclampsia with thrombophilia in Africa including Sudan.MethodsA case –controls study was conducted at Saad Abualila Hospital in Khartoum, Sudan during the period of February through November 2017. The cases were women with preeclampsia and healthy pregnant women were the controls (180 women in each arm of the study). Genotyping for Factor-V Leiden 1691G/A and Prothrombin gene variation 20210G/A was done by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP).ResultsThere was no significant difference in the age, parity, body mass index (BMI) and the other characteristics between the cases and the controls. Genotypes distribution of Factor V Leiden 1691G/A and prothrombin gene 20210G/A in controls was in accordance with the Hardy–Weinberg equilibrium (P > 0.05). The factor V Leiden-variation was present in 9.6% of the cases compared with 0.6% of the controls, P < 0.001 (OR = 18.60, 95% CI = 2.38–136.1). Only 4 patients with severe preeclampsia had homozygous variation A/A and it was not detected in the controls. Prothrombin G20210A variations not detected neither in the cases nor in the controls group.ConclusionsHigh prevalence of Factor V Leiden 1691G/A variation in preeclamptic patients compared to controls suggest an involvement of this variation in predisposing to preeclampsia in this setting.

Genetic correlation between Prothrombin G20210A polymorphism and retinal vein occlusion risk.

The aim of this study was to perform an updated meta-analysis to quantitatively investigate the association between G20210A polymorphism of Prothrombin gene and the risk of retinal vein occlusion (RVO), based on the available publications with inconsistent results. We utilized the Stata software to perform the heterogeneity test, association test, Begg's and Egger's tests, and sensitivity analysis. We searched three on-line databases (PubMed, Embase, and WOS) and obtained a total of 422 articles. Based on our selection criteria, 24 case-control studies were finally enrolled in this overall meta-analysis; a subgroup analysis by the factors ethnicity, control source, and RVO type was done. Through the association test of overall meta-analysis, we did not observe a significant difference between RVO cases and controls under the A vs G (allele) (z=1.49, P=0.137), A vs G (carrier) (z=1.42, P =0.155), GA vs GG (z=1.50, P=0.135), and GA+AA vs GG (z=1.50, P=0.135). Furthermore, we observed similar negative results in the association test of subgroup analysis (all P>0.05). Heterogeneity, Begg's, and Egger's tests excluded the presence of high heterogeneity and publication bias. Statistically stable results were observed in the sensitivity analyses. Based on integrated analysis of the current evidence, Prothrombin gene G20210A polymorphism is likely unrelated to the risk of RVO.

Prothrombin G20210A polymorphism in patients with venous and cryptogenic arterial strokes among ethnic groups in south and north India.

Prothrombin (PT) G20210A is one of the genetic polymorphisms associated with thrombophilia. Studies show a low prevalence for this polymorphism in Asian populations with only one subject reported from India. We studied the prevalence and association of this polymorphism in patients with arterial and venous strokes and their matched controls in south and north India. We recruited patients with cerebral venous thrombosis (mean age 37.2 years) and cryptogenic ischaemic stroke (mean age 36.7 years), and age- and sex-matched controls (mean age 37.6 years) from south and north India. Genotyping was carried out using polymerase chain reaction followed by restriction fragment length polymorphism, and the prevalence of the variants among the patients and controls was compared. The heterozygous allele of the polymorphism was detected in both groups with significantly higher prevalence among north Indians (5/154; 3.2%) compared with south Indians (4/516; 0.8%; p = 0.026). Thrombosis as a manifestation of this polymorphism was more among north Indians with 4/82 (4.9%) of patients with ischaemic stroke and cerebral venous thrombosis having this polymorphism compared with south Indian patients 1/72 (1.4%), p = 0.003. PT G20210A is prevalent in India, especially among those from north India. Its role in predisposition to thrombosis needs to be studied further along with other known risk factors.

Prothrombotic genotypes and risk of venous thromboembolism in cancer

Venous thromboembolism (VTE) is a common and potentially life-threatening complication in cancer. Patients with cancer are at a higher risk of VTE-related complications such as major bleeding during anticoagulant treatment, recurrence and mortality. Therefore, it is important to identify cancer patients with high risk of VTE in order to implement targeted prevention to those with a favorable benefit-to-harm ratio for thromboprophylaxis. VTE is strongly heritable, and during the last decades, several prothrombotic genotypes associated with VTE-risk have been identified. However, most of these studies were conducted in non-cancer patients, and the role of prothrombotic genotypes in cancer-related VTE is scarcely studied. In this review, we summarize current knowledge on the role of prothrombotic genotypes in cancer-related VTE, with particular focus on factor V Leiden, the prothrombin G20210A mutation and polymorphisms in the ABO gene. In general, many of the studies were small and performed in selected cancer populations, and they showed somewhat diverging results. Results from recent, larger, studies indicated that there is an association between these prothrombotic genotypes and cancer-related VTE. However, their predictive capability has not been assessed and the clinical implications are yet unclear. Future research should be conducted in larger cancer patient populations, and should be extended to include recently identified prothrombotic genotypes and assess the predictive value of genetic risk scores.

Association of Factor V Leiden and Prothrombin G20210A Polymorphisms in Women with Recurrent Pregnancy Loss in Isfahan Province, Iran.

Background:Maternal thrombophilia has been identified as a risk factor for recurrent pregnancy loss (RPL). The aim of this study was to investigate the association between prothrombin G20210A and factor V Leiden (FVL) polymorphisms in women with RPL and a control group of parous women in Isfahan province of Iran.Methods:We studied 250 women with idiopathic RPL and 116 control cases. Prothrombin and FVL different genotypes were determined using polymerase chain reaction and reverse hybridization technique.Results:The frequencies of heterozygous mutation prothrombin G20210A were 6% and 0.9%, respectively (P = 0.025), in cases compared to the control group. The frequencies of homozygous mutation prothrombin G20210A were 0.4% and 0%, respectively, in cases compared to controls (P = 0.02). The prothrombin mutation was significantly higher in cases compared to the control group (odds ratio 8.81; 95% confidence interval: 1.16–66.62). There was no significant difference between the FVL mutation and pregnancy loss.Conclusions:The results indicated a significant higher frequency of prothrombin G20210A in women with RPL in comparison with controls. Our data suggest that the prothrombin G20210A mutation, but not the FVL mutation, may be an unrecognized cause of RPL in our population.

Prothrombin G20210A (rs1799963) polymorphism increases myocardial infarction risk in an age-related manner: A systematic review and meta-analysis

G20210A polymorphism (rs1799963) within the prothrombin gene is associated with a higher circulation level of prothrombin, thus increasing the likelihood of developing myocardial infarction (MI). Opinions differ regarding the correlation between prothrombin G20210A genotype and MI risk, which prompted us to conduct a meta-analysis to determine this association. PubMed, EMBASE, Web of Science and CNKI were searched for pertinent reports. A total of 34 studies involving 14 611 MI cases and 84 358 controls were analyzed in this quantitative analysis. We found a statistically significant association between prothrombin G20210A polymorphism and MI in the allele model (A vs. G, OR = 1.43, 95%CI: 1.18–1.72), heterozygote model (GA vs. GG, OR = 1.41, 95%CI: 1.16–1.72) and dominant model (GA + AA vs. GG, OR = 1.41, 95%CI: 1.15–1.72). The association remains significant in Caucasians but not in non-Caucasians. Moreover, prothrombin G20210A polymorphism increases MI risk in an age-related manner. A further significant association was found in a subpopulation younger than 55 years (allele model, OR = 1.76, 95%CI: 1.32–2.35; heterozygote model, OR = 1.70, 95%CI: 1.24–2.33; dominant model, OR = 1.70, 95%CI: 1.24–2.34). Sensitivity analysis and publication bias analysis revealed stable and statistically robust results. Our meta-analysis demonstrated that prothrombin G20210A polymorphism may represent a risk factor for MI.

Thrombophilia genetic testing in Romanian young women with acute thrombotic events: role of Factor V Leiden, Prothrombin G20210A, MTHFR C677T and A1298C polymorphisms / Evaluarea genetică a trombofiliilor la femei tinere din România cu evenimente acute trombotice: rolul Factorului V Leiden, Protrombinei G20210A, polimorfismelor MTHFR C677T și A1298C

Abstract Objective: The present case-control study aimed at evaluating the contribution of thrombophilic polymorphisms to acute venous (VTE) as well as arterial thrombotic events (ATE) in a population of young women with few traditional thrombotic factors (CVRF). Methods: We consecutively enrolled patients under 45 years of age, with less than 3 CVRF, evaluated for VTE or ATE, women and men as a comparator. The control group consisted of healthy young women. A thrombophilia panel and genetic testing for Factor V Leiden (FVL), G20210A Prothrombin and MTHFR polimorphisms were done. Results: A total of 323 persons were enrolled: 71 women and 121 men with thromboembolic events, and 131 healthy female as controls. Hyperhomocysteinemia was more frequent in ATE (30.4%) than VTE female patients (6.25%), p&lt;0.01. Genetic testing was available in 45 women and 84 men with acute thrombotic events and in all controls. Homozygous FVL was associated with VTE in young women (10.3% vs 0% controls, p&lt;0.01). Prothrombin G20210A polymorphism had the lowest prevalence – 5.4% and only heterozygosity was found. MTHFR C677T heterozygosity showed no significant difference between women patients and controls (62.2 % vs 43.5% respectively, p=0.1). The homozygous status, less frequent (6.6%), was not associated with ATE or VTE. Homozygous MTHFR A1298C was associated with VTE in women (17.2% patients vs 4.5% controls, OR 4.34, p 0.02, CI 1.22-15.3). Conclusion: In young women with few CVRF, mild hyperhomocysteinemia, homozygosity for FVL and for MTHFR A1298C polymorphisms increase the risk for VTE but not ATE. MTHFR polymorphisms are found with increased frequency in both healthy persons and patients therefore, their significance as an important thrombotic risk modifier remains unclear.

Alterations in Platelet Activity and Elastic Modulus of Healthy Subjects, Carriers of G20210A Polymorphism in the Prothrombin Gene

Summary Platelet activation is a complex process in which platelet reorganization takes place associated with changes in the cell shape, topology, membrane elasticity and microparticle production. The aim of this study was to investigate the changes/aberrations in the platelet activity, elasticity and morphology in healthy subjects, carriers of A allele of prothrombin G20210A polymorphism. Blood samples from 18 healthy subjects were used for platelet analysis by force-mode atomic force microscopy. Restriction analysis was used to investigate the carriage of G20210A polymorphism in the prothrombin gene. Flow- cytometry was applied to evaluate platelet activation. Young’s modulus of the plasma membranes of platelets derived from healthy subjects, carriers of variant A allele of prothrombin 20210G&gt;A polymorphism (407±69 kPa) is two times higher than the one determined for non­carriers (195.4±48.7 kPa; p&lt;0.05). The background activity of platelets measured as an interrelation of Cd41/Cd61 and CD62 by flow cytometry was also higher in carriers of variant A allele of prothrombin 20210G&gt;A polymorphism (5.0%) than in non-carriers (1.3%). Platelets isolated from healthy carriers of variant A allele of prothrombin 20210G&gt;A polymorphism exhibited a higher level of activity and a higher degree of stiffness at the stage of spreading as compared to platelets from non­carriers.

Association Between the G20210A Polymorphism of Prothrombin Gene and Myocardial Infarction in Tunisian Population.

The prothrombin is the precursor of the serine protease thrombin, a key enzyme in homeostasis. Prothrombin G20210A polymorphism (rs1799963) was described as a moderate risk factor for venous thrombosis because this mutation is associated with prothrombin elevated levels which may lead to an imbalance between the procoagulant, anticoagulant, and fibrinolytic system. 20210A carriers have an increased risk of thrombosis. In this study, we proposed to determine the prevalence of 20210A prothrombin variant among Tunisian population, and to evaluate the potential relevance of this variant with myocardial infarction. This study included 1290 unrelated Tunisians (1007 male and 283 female) divided in two groups: Four hundred and eighty-seven MI patients (mean age: 52.64±8.98years) and 803 apparently healthy controls (mean age: 51±8.99). The prothrombin G20210A polymorphism was carried out by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) analysis. The distribution of genotypes was in accordance with Hardy-Weinberg equilibrium (p>0.05). A significant difference in genotype distribution and allele frequency was observed between patients and controls. Male patients with MI had a frequency of 97% for GG genotype and 3% for GA+AA genotypes. The control group had a frequency of 99% for the GG genotype and 1% for the GA+AA genotypes which is significantly lower than the frequency found in patients (p=0.01). The same genotype frequencies were found in women (p=0.032). The MI patient group showed a significantly higher frequency of 20210A allele compared to controls 0.02 versus 0.01 [OR=3.60 (95% CI=1.29-10.53), p=0.005] in men and 0.015 versus 0.068 [OR=4.68 (95% CI=1.60-14.26), p=0.001] in women. Our work showed a significant but not independent association between the G20210A polymorphism of the prothrombin gene and MI in the Tunisian population.