Prothrombin Gene Polymorphism Research Articles

Factor V Leiden, prothrombin, MTHFR, and PAI-1 gene polymorphisms in patients with arterial disease: A comprehensive systematic-review and meta-analysis

IntroductionThe role of inherited thrombophilia in arterial disease is uncertain. We performed a systematic-review and meta-analysis of inherited thrombophilia in cerebrovascular (CVD), coronary heart (CHD), and peripheral artery disease (PAD) patients. Materials and methodsMEDLINE and EMBASE were searched up to February 2022. Pooled prevalences (PPs) and odds ratios (ORs) with 95 % confidence intervals (95%CI) were calculated in a random-effects model. Factor V Leiden (G1691A), prothrombin (G20210A), MTHFR C677T/A1298C and PAI-1 4G/5G were evaluated. Results377 studies for 98,186 patients (32,791 CVD, 62,266 CHD, 3129 PAD) and 108,569 controls were included. Overall, 37,249 patients had G1691A, 32,254 G20210A, 42,546 MTHFR C677T, 8889 MTHFR A1298C, and 19,861 PAI-1 4G/5G gene polymorphisms. In CVD patients, PPs were 6.5 % for G1691A, 3.9 % for G20210A, 56.4 % for MTHFR C677T, 51.9 % for MTHFR A1298C, and 77.6 % for PAI-1. In CHD, corresponding PPs were 7.2 %, 3.8 %, 52.3 %, 53.9 %, and 76.4 %. In PAD, PPs were 6.9 %, 4.7 %, 55.1 %, 52.1 %, and 75.0 %, respectively. Strongest ORs in CVD were for homozygous G1691A (2.76; 95 %CI, 1.83–4.18) and for homozygous G20210A (3.96; 95 %CI, 2.05–7.64). Strongest ORs in CHD were for homozygous G1691A (OR 1.68; 95%CI, 1.02–2.77) and G20210A (heterozygous 1.49 95%CI, 1.22–1.82; homozygous 1.54 95%CI, 0.79–2.99). The OR for PAI-1 4G/4G in PAD was 5.44 (95%CI, 1.80–16.43). Specific subgroups with higher PPs and ORs were identified according to age and region. ConclusionsPatients with arterial disease have an increased prevalence and odds of having some inherited thrombophilia. Some thrombophilia testing may be considered in specific subgroups of patients.

Prothrombin Gene Polymorphism (G20210A) among Sudanese Patients with Intracerebral Hemorrhage, Khartoum State, 2022

Background 
 Intracranial hemorrhage is the third most frequent cause of cerebrovascular disease, also known as cerebral bleed, intraparenchymal bleed and hemorrhagic stroke. This study was designed to detect the possible present of factor II polymorphism (G20210A) among Sudanese patients with Intercereberal hemorrhage.
 Material and method
 This study was cross sectional hospital-based study,conducted at the research laboratory of the national center of neurological sciences (NCNS), Khartoum, Sudan during the period June 2022 to August 2022.It included all patients attended with intracerebral hemorrhage, demographic data ( age , gender, associated disease ). DNA extraction was done from blood of all patients and control.PCR for factor prothrombin gene was done and thus Sanger sequencing.
 Results:
 The PCR results showed; 100% positive forfactor II gene. And sequencing result showed base bare exchange in factor II gene G to A (G20210A)polymorphism .
 Conclusion
 Factor II gene polymorphism (G20210A) was detected and might be association with Intercereberal hemorrhage among Sudanese patients

The Association of Prothrombin Gene Mutations and Cytomegalovirus Infection with Abortion Among Iraqi Women

Abortion is categorized as the termination of conception caused by the failure or removal of the embryo from the uterus before the conclusion of pregnancy. Microorganisms and genetic factors are two of the many factors associated with abortion. Cytomegalovirus is a widespread congenital virus infection pathogen that affects a wide variety of people. The prothrombin gene is one of the essential causes that trigger blood clotting and the function of abortion women, therefore the aim of the study is to detect and associate Cytomegalovirus and prothrombin gene mutation (Gene ID: 14061 in NCBI) with abortion through genetic and immunological methods. Five ml of whole blood was collected from an intravenous puncture and divided into two tubes, one with EDTA and one without (plain tube) from 74 women with an abortion history as a patient group and 74 women without an abortion record who had at least one successful fertility as a control group. Allele-specific PCRs are used to amplify gene regions with genetic primers containing prothrombin gene polymorphisms. Current results have shown the greatest risk of abortion was observed in women patients with IgG seropositivity in 65 women with frequency (87.8%) and the lowest rate of abortion was in IgM seropositivity in 3 women with frequency (4.1%) and 6 (8.1%) were positive for IgM-and IgG indicating they have both an old and recent infections. Furthermore, allele-specific PCRs are used to amplify prothrombin G20201A polymorphism. The result of this study demonstrated there is no association between prothrombin genotype level frequency and abortion in CMV-infected women. While, there is a highly significant association between A and G Alleles combinations and abortion in CMV-infected women.

Prevention of recurrent fetal growth retardation in patients with circulating antiphospholipid antibodies and genetic thrombophilia

Aim: to evaluate the effectiveness of using low molecular weight heparin (LMWH) and low-dose acetylsalicylic acid (ASA) in preventing recurrence of early and late fetal growth retardation (FGR) in patients with antiphospholipid syndrome (APS) and/or genetic thrombophilia.Materials and Methods. A prospective randomized controlled study was conducted by examining 32 patients aged 23 to 43 years with a history of early and late II and III FGR as well as thrombophilia. Prevention protocol using LMWH and ASA was carried out from the pregravid period or early pregnancy. The control group included 35 women with uncomplicated pregnancy. Antiphospholipid antibodies (APA) were measured according to the Sydney antiphospholipid syndrome (APS) criteria by using enzyme immunoassay (ELISA): cardiolipin, β2-glycoprotein 1 and additionally antibodies to annexin V, prothrombin, etc. (IgG/IgM isotypes); lupus anticoagulant – by a three-stage method with Russell's viper venom; antithrombin III and protein C levels – by chromogenic method; prothrombin gene polymorphisms G20210A as well as factor V Leiden polymorphism – by chain reaction; homocysteine – by ELISA.Results. It was found that prevention protocol was effective in 78.1 % cases. FGR re-developed in 7 (21.9 %) pregnant women: in 2 (6.3 %) at 20 and 22 weeks, in 3 (9.4 %) at 30–32 weeks, in 2 (6.3 %) after 34 weeks of pregnancy. All these patients were found to have APA exceeding 40 U/ml with low dynamics of decline, 3 (9.4 %) were older than 35 years, 2 (6.3 %) had chronic kidney pathology and 1 (3.1 %) had a hypertension in the anamnesis.Conclusion. The use of LMWH and low-dose ASA starting from the pre-pregnancy period and early pregnancy as a part of complex therapy allows to effectively prevent re-development of FGR in patients with thrombophilia. In case of high APA titers, the use of LMWH and low-dose ASA may be ineffective, and alternative treatment methods in addition to anticoagulant therapy should be used to improve obstetric results.

Antiphospholipid antibodies, genetic thrombophilia and fetal growth retardation

Aim: to study the role of antiphospholipid antibodies (AРA) and genetic thrombophilia as a potential cause of the development or a component in the pathogenesis of early and late fetal growth retardation (FGR).Materials and Methods. There was conducted a prospective randomized controlled trial with 118 women enrolled. The main group consisted of 83 patients, whose pregnancy was complicated by FGR degrees II and III, stratified into two groups: group 1 – 36 pregnant women with early FGR, group 2 – 47 pregnant women with late FGR. Women were subdivided into subgroups according to the FGR severity. The control group consisted of 35 pregnant women with a physiological course of pregnancy. АРА were determined according to the Sydney antiphospholipid syndrome criteria by enzyme immunoassay (ELISA): against cardiolipin, β2 -glycoprotein 1, annexin V, prothrombin, etc. (IgG/IgM isotypes); lupus anticoagulant – by the three-stage method with Russell's viper venom; antithrombin III and protein C levels – by chromogenic method; prothrombin gene polymorphisms G20210A and factor V Leiden – by polymerase chain reaction; homocysteine level – by ELISA.Results. AРA circulation (medium and high titers), genetic thrombophilic defects and/or hyperhomocysteinemia were detected in 40 (48.2 %) patients with FGR, which was significantly higher than that in the control group (p < 0.05): in group 1 (41.7 % of women) AРA (30.6 %) and AРA with genetic thrombophilia or hyperhomocysteinemia (11.1 %) were revealed; in group 2 (51.1 % of women) AРA (21.3 %), AРA with hyperhomocysteinemia (4.3 %), genetic thrombophilia (25.5 %), and due to hyperhomocysteinemia (2.1 %) were found. No differences in prevalence of thrombophilia rate in patients were observed related to FGR severity, but a correlation between the FGR severity and AРA titers was found.Conclusion. Testing for the presence of AРA, genetic thrombophilia and hyperhomocysteinemia should be recommended for patients with FGR (including those with FGR in medical history), especially in the case of its early onset. It is recommended to determine the full AРA spectrum.

Association of VEGFA, factor V and prothrombin gene polymorphisms with early pregnancy loss

Association of VEGFA, factor V and prothrombin gene polymorphisms with early pregnancy loss

Association of prothrombin, FV Leiden and MTHFR gene polymorphisms in the Montenegrin patients with venous thromboembolism

Background/Aim. Polymorphisms of the factor V Leiden (FV G1691A), prothrombin (FII G20210A), and methylene-tetrahydrofolate reductase (MTHFR C677T) genes are the most commonly investigated inherited risk factors for developing venous thromboembolism (VTE). Despite this fact, there is insufficient data regarding their clinical burden and distribution in the Montenegrin population. The aim of the study was to determine the frequency of these polymorphisms in Montenegrin patients with VTE. Methods. This case-control study was conducted on 160 Caucasian subjects. The study group was composed of 80 patients (35 men and 45 women) with VTE. The control group consisted of 80 healthy individuals (32 men and 48 women) without previous thromboembolic episodes. Genotyping of the FV G1691A, FII G20210A, and MTHFR C677T polymorphisms was per-formed by allele-specific polymerase chain reaction (PCR). Results. The frequency of heterozygotes (HET) for FII G20210A and FV G1691A was significantly higher in the VTE group compared to the healthy control group (?2 = 11.7; p = 0.001 and ?2 = 17.69; p < 0.001, respectively). The association of FII G20210A and FV G1691A polymorphisms with an increased risk of VTE [odds ratio (OR) 10.5; 95% confidence interval (CI) = 2.34 to 47.27, and OR 14.8; 95% CI = 3.34 to 65.43; p < 0.001, respectively] was confirmed. Recessive homozygotes (RH) for FII G20210A and FV G1691A were not found in any of the investigated groups. Regarding MTHFR C677T, the difference between the frequency of HET and RH in the control and VTE group was not significant. Conclusion. Our study showed that FII G20210A and FV G1691A polymorphisms are significantly associated with VTE. Detection of the above-mentioned polymorphisms prior to VTE development can contribute to the prevention of further VTE occurrence, especially among patients' relatives who are carriers of these polymorphisms.

A Study on the Role of Thrombophilic Genetic Disorders as a Risk Factor for Thrombotic Complications in Patients with Myeloproliferative Disorders

Summary Myeloproliferative neoplasms (MPN) are haematological diseases, characterized by clonal hematopoiesis. Hemostasis abnormalities are among the most critical and frequent complications, affecting the quality of life and a possible reason for death. Thrombotic complications are common and multifactorial. Our aim was to study some genetic thrombophilia factors – Factor V Leiden (FVL), G20210A mutation in prothrombin gene (PR G20210A) and PLA2 allele polymorphism of glycoprotein IIIa gene (GPIIIa gene), and their frequency and association with thrombotic risk in both Philadelphia-positive and Philadelphia-negative MPN – chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary and secondary myelofibrosis (MF). In our patient population, PLA2 allele polymorphism of GPIIIa gene proved to be the most common and significantly associated with thrombotic complications – 26.85% of our patients were carriers, and 24.14% of them reported thrombotic complications.

The role of polymorphism of hemostatic system genes in the risk assessment of the surgical treatment of chronic thromboembolic pulmonary hypertension

Aim . To assess polymorphisms of the hemostatic system genes in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and their influence on the results of thrombendarterectomy from the branches of the pulmonary artery. Material and methods . The study included 70 people with verified CTEPH who underwent thrombendarterectomy from the branches of the pulmonary artery. We studied the prevalence of polymorphisms of the hemostatic system genes (F2: 20210 G>A; F5: 1691 G>A (Arg506Gln); F7: 10976 G>A (Arg353Gln); F13: G>T (Val34Leu); FGB: 455 G>A; ITGA2: 807 C>T (Phe224Phe); ITGB3: 1565 T>C (Leu33Pro); SERPINE1 (PAI-1): 675 5G>4G) and their relationship with the immediate and long-term results of surgical treatment. Results . One or several polymorphisms of the hemostasis system genes were registrated in 98% of cases in the group with CTEPH. The most common polymorphism of the SERPINE1 (PAI-1) gene was 675 5G>4G (in 80% of cases). Mutation of the F2 gene: 20210 G>A was noted in 14% of patients, F5: 1691 G>A (Arg506Gln) - 13%, F7: 10976 G>A (Arg353Gln) - 11%, F13: G> T (Val34Leu) - 34 %, FGB: 455 G> A - 35%, ITGA2: 807 C>T (Phe224Phe) - 48%, ITGB3: 1565 T>C (Leu33Pro) - 24%. The only factor influencing the results of surgical treatment was the polymorphism of the prothrombin gene (20210 G>A), which showed a high predictive value in assessing the risk of respiratory failure in the early postoperative period of thrombendarterectomy from the branches of the pulmonary artery (OR 3,5 (1,7-18,8) p=0,041). Other genetic disorders of the hemostatic system did not show significant associations with the outcome of surgical treatment. Conclusion . We showed the relationship between the presence of prothrombin gene polymorphism (20210 G>A) and the increased risk of respiratory failure in the early postoperative period of thromboendarterectomy from the branches of the pulmonary artery. Other genetic disorders of the hemostatic system and their carriage did not show significant associations with the outcome of surgical treatment.

Association Between the 20210G>A Prothrombin Gene Polymorphism and Arterial Ischemic Stroke in Children and Young Adults—Two Meta-analyses of 3586 Cases and 6440 Control Subjects in Total

BackgroundPrevious data have shown that the 20210G>A polymorphism of the Factor II gene is related to an increased prothrombin level, which may in turn lead to a procoagulant state. The heterogeneous and multifactorial character of arterial ischemic stroke often results in contradictory reports describing the association between the 20210G>A polymorphism and arterial ischemic stroke in different populations. We performed a meta-analysis of available data addressing the relation between the FII 20210G>A polymorphism and arterial ischemic stroke, both in young adults and children. MethodsWe searched PubMed using appropriate keywords. The inclusion criteria for the study were as follows: case-control study, study population consisting of children, study population consisting of young adults, arterial ischemic stroke confirmed by magnetic resonance imaging or computed tomography, and English language. The exclusion criteria included lack of genotype or allele frequencies, study design other than a case-control study, outcome definition other than arterial ischemic stroke, and previously overlapped patient groups. Finally, 30 case-control studies (14 in children and 16 in young adults) were included. Statistical analyses were conducted using R software. Heterogeneity between the studies was evaluated using the Dersimonian and Laird's Q test. In the case of significant between-studies heterogeneity, the pooled odds ratio was estimated with a random-effects model, otherwise a fixed-effects model was used. ResultsThe pooled analysis showed that carriers of 20210A allele (GA+AA genotypes) of the prothrombin gene are more common in arterial ischemic stroke patients, both in children and young adults, than in control subjects (P = 0.006; odds ratio, 1.83; 95% confidence interval, 1.19 to 2.80 and P = 0.001; odds ratio, 1.69; 95% confidence interval, 1.25 to 2.28, respectively). ConclusionsThe results of the present meta-analysis have proven that the FII 20210G>A polymorphism is associated with arterial ischemic stroke in both pediatric and young adult patients.

Mutations in the Gene for Factor V Leiden and G20210A Prothrombin Polymorphism in Women With Recurrent Spontaneous Abortion: A Retrospective Study in a Brazilian Population

Background: Pregnancy is sufficiently considered an important risk factor for thromboembolic events. We aimed to determine the prevalence of factor V Leiden (FVL) and prothrombin gene 20210A mutations in patients with miscarriages and to correlate these results with normal and abnormal karyotypes. Methods: A retrospective study was carried out in 247 women with a history of miscarriages. These samples were karyotyped, and the DNA was extracted (chorionic villi) and genotyped for FVL and prothrombin gene polymorphism. Results: Polymorphism frequency was compared among different groups. FLV showed significant levels in the normal cytogenetic groups in two comparisons: normal abortion (NA) versus abnormal abortion (AA) (P = 0.08) and normal recurrent abortion (NRA) versus AA (P = 0.048). The presence or absence of at least one polymorphism was evaluated. The frequency of G20210A prothrombin gene polymorphism was higher in NA than in AA: NA versus AA (P = 0.014), NRA versus AA (P = 0.018) and AA versus NRA (P = 0.01). Conclusions: The FVL showed probable importance in the genesis of abortions due to its greater frequency of normal karyotype miscarriage. Once presence of both polymorphisms was significantly higher in normal karyotype miscarriage than in abnormal, we can infer that the alterations are associated with the pathophysiology of abortions. J Clin Gynecol Obstet. 2016;5(3):85-91 doi: http://dx.doi.org/10.14740/jcgo412e

Factor V Leiden 1691G/A and prothrombin gene 20210G/A polymorphisms as prothrombotic markers in adult Egyptian acute leukemia patients.

Factor V Leiden 1691G/A and prothrombin gene 20210G/A mutations are the most common genetic defects leading to thrombosis. This work aimed to study the FV Leiden and the prothrombin gene polymorphism in adult Egyptian patients with acute leukemia and their importance in thrombophilia screening. The study included 76 patients with acute leukemia and 100 healthy controls. Genotyping was done by real-time polymerase chain reaction technique. For factor V Leiden, the frequency of G/A mutation conferred more than 2.5-fold of increased risk of (OR 2.639 95 % CI 1.045-6.669). The frequency of factor V Leiden combined (G/A + A/A) genotypes conferred 2.83-fold of increased risk (OR 2.828, CI 1.13-7.075), The A allele conferred almost threefold increased risk (OR 2.824, 95 % CI 1.175-6.785). Despite higher frequency in patients compared to controls, there was no risk of association between prothrombin gene mutation and acute leukemia in adult Egyptians nor was there between combined genotypes of prothrombin gene mutation and factor V Leiden.

Comparative Study on the Effect of Factor V Leiden and Prothrombin Gene Polymorphism in Preeclampsic Cases

Objective: To identify polymorphism of Factor V Leiden and Prothrombin gene in women suffering from preeclampsia. Study design: From 142 pregnant women we identified 92 women suffering from preeclampsia and 50 healthy controls with normal pregnancy matched for age and socioeconomic status, preeclampsic patient classified as mild preeclampsia 42(45.7%) and severe preeclampsia 50(54.3%). Blood samples were tested for DNA polymorphism affecting thrombophilia Factor V Leiden and Prothrombin gene polymorphism. Results: Heterozygous AG genotype showed a significant high frequency among preeclampsic patients (20.7%) compared to controls (4.0%), (OR 6.2, P= 0.006) regarding to Prothrombin gene but: Factor V Leiden, AG genotype showed (8.7%) of preeclampsic patients which was absent in any of the controls.

Comparative Study on the Effect of Factor V Leiden and Prothrombin Gene Polymorphism in Preeclampsic Cases

Comparative Study on the Effect of Factor V Leiden and Prothrombin Gene Polymorphism in Preeclampsic Cases

Association between prothrombin gene polymorphisms and hereditary thrombophilia in Xinjiang Kazakhs population

To assess the association between polymorphisms of prothrombin gene and hereditary thrombophilia in Xinjiang Kazakhs population. Through cross-sectional investigation, permanent Kazakh population of Ili Kazakh Autonomous Prefecture was selected as the study object to measure their antithrombin III (AT-III), protein C, protein S activity and activated C protein resistance value, thus defining the situation of the crowd's hereditary thrombophilia. Sequenom Massarray detection technology was used to conduct a genotype test of the six sites selected by the case and control groups. Haploview software was used to perform linkage disequilibrium analysis of the six sites, and the impact of the interaction between genetic variations and environment on hereditary thrombophilia was researched by the use of sum model. A total of 1005 Kazakh volunteers participated in the test (332 men and 673 women), average age (41.13 ± 11.50) years; the prevalence of hereditary thrombophilia in Xinjiang Kazakh population was 31.0%, and the prevalence of AT-III deficiency, protein C deficiency, protein S deficiency and activated protein C resistance was 16.4, 14.9, 20.6 and 7.8%, respectively. The difference in allele frequency of the hereditary thrombophilia patient group at rs3136447 and rs5896 sites was statistically significant (P = 0.0483 and P = 0.0302, respectively). rs5896 and rs2070852 had high linkage disequilibrium (r = 0.99), and constituted a single-domain block 1. The rs3136447 and the rs5896 polymorphisms located in the region of the prothrombin gene may be associated with hereditary thrombophilia in the Xinjiang Kazakhs population. There is additive interactive effect of rs5896 polymorphism (CT + TT) and smoke on hereditary thrombophilia.

Influence of proband's characteristics on the risk for venous thromboembolism in relatives with factor V Leiden or prothrombin G20210A polymorphisms

AbstractIn family studies, the risk for venous thromboembolism (VTE) in relatives with factor V Leiden (FVL) or G20210A prothrombin (PT20210A) gene polymorphisms may differ according to genotype and clinical presentation of the proband. To address this hypothesis, a retrospective cohort family study was carried out on 192 kindreds with at least one member with homozygous FVL or PT20210A, for a total of 886 relatives. The proband of the family was heterozygous in 68 and homozygous or with both polymorphisms in 124 kindreds. Twenty-three probands were asymptomatic, 11 had had arterial thrombosis, 7 obstetrical complications, and 151 venous thrombosis (122 VTE and 29 superficial vein thrombosis). The incidence of VTE (per 1000 patient-years) in relatives was higher when the proband had heterozygous rather than homozygous polymorphism (1.25 [95% confidence interval (CI), 0.73-1.91] vs 0.44 [0.19-0.78]) and when the proband had had VTE instead of other or no clinical manifestations (0.95 [0.57-1.42] vs 0.50 [0.19-0.96]). Compared with relatives belonging to kindreds with homozygous probands without VTE, the adjusted hazard ratio of VTE for relatives selected from kindreds with heterozygous probands with VTE was 4.14 (95% CI, 1.17-14.71). The genotype and clinical presentation of the proband influence the risk for VTE in relatives with FVL or PT20210A.

The 20210G>A and 19911A>G polymorphisms of prothrombin gene and recurrent miscarriages

The aim of the study was to evaluate the frequency of 20210G>A and 19911A>G prothrombin gene polymorphisms in a group of women with 2 or more miscarriages in the first trimester of pregnancy The study involved 150 women with two or more miscarriages in the first trimester of pregnancy (mean age 31.5 +/- 4.1 years). The control group consisted of 180 healthy women (mean age 28.7 +/- 4.0 years). The frequency of genotypes and alleles of the investigated polymorphisms was evaluated by polymerase chain reaction/restriction fragments length polymorphism method (PCR/RFLP). As to the 20210G>A prothrombin gene polymorphism, overrepresentations of 20210GA genotype have been observed in the group of women with miscarriages (2.7% vs. 1.1% in the control group, WR = 2.44, ns), as well as overrepresentation of 20210A allele (1.3% vs. 0.6% in the control group, WR = 2.42, ns). Considering the 19911A>G polymorphism, a similar frequency of mutated homozygous 19911GG genotype has been noted (22.6 vs. 21.1% in controls, OR= 1.10, ns). Also, frequency of mutated 19911G allele was similar in both investigated groups with miscarriages and controls (48.6% vs. 45.7%, OR = 0.89, ns). Our findings suggest lack of correlation of 20210G>A and 19911A>G prothrombin gene polymorphisms with the risk of recurrent miscarriages in the first trimester of pregnancy Further studies, concerning other genetic variants conditioning inherited thrombophilia and environmental factors influencing the risk of recurrent abortions, are needed. Therefore, further research with more numerous group of women with recurrent miscarriages and taking into account other polymorphisms of thrombophilia and influence of environmental factors is required.

Myocardial infarction marker levels are influenced by prothrombin and tumor necrosis factor-α gene polymorphisms in young patients

Polymorphisms of genes encoding key factors for the control and activation of inflammatory response and coagulation cascade regulation may play a role in genetic susceptibility to acute myocardial infarction (AMI). This study sought to analyze the effect of TNF −308G/A and pro-thrombin (FII) 20210G/A polymorphisms on the laboratory parameters of young patients affected by AMI. Results indicated that TNF −308A positive genotype frequencies were increased in these patients and that a genetically determined higher production of TNF-α is associated in young subjects to a more severe cardiac damage as depicted by higher levels of troponin, Creatine kinase-MB Isoenzyme (mCK-MB) and a significant increased plasma fibrinogen levels. Similar and probably additive effects on might have a genetically determined increased production of pro-thrombin even if no significant differences in genotype frequencies of pro-thrombin (FII) 20210G/A polymorphisms were observed in this study. All together these results, indicating the relationship among genetically determined TNFα and FII production and increased levels of tissue damage markers of AMI, suggest that a complex genetic background, might be involved in susceptibility to AMI in young men influencing the extension and severity of the disease.

Should factor V Leiden mutation and prothrombin gene polymorphism testing be done in women with recurrent miscarriage from North India?

Role of thrombophilic factor (FV) in the etiology of recurrent miscarriages is not confirmed till date. It has been hypothesized that thrombophilic G1691A factor V Leiden (FVL), if detected well ahead in time among recurrent miscarriages may be a treatable. The role of FVL mutation in the pathogenesis of sporadic and recurrent miscarriages among North Indian women was studied to construct the frequency data in this part of the country. Further, we have evaluated the cost-benefit factor. This is a case-control study, women with recurrent miscarriages (n = 1,000) as cases and healthy parous women (n = 500) as controls were enrolled in the study between January 2003 and January 2012. DNA was extracted from peripheral blood and analyzed for the presence of FVL mutation and prothrombin gene polymorphism (G20210A). We have carried out the meta-analysis taking into consideration 20 other world populations. In total, 50 (5.0 %) cases and 12 (2.4 %) controls were heterozygous for the FVL mutation. The incidence of FVL was higher in recurrent miscarriage cases as compared to the control group (OR 2.14; 95 % CI 1.12-4.05). Our results revealed the absence of FVL mutation in a homozygous state among patients and controls. Although the heterozygous mutation is almost double in cases as compared to controls, we still suggest that looking at the cost-benefit analysis this test may not be included in the battery of tests performed on recurrent miscarriages among North Indians from this part of the country.

Atypical timing and presentation of periventricular haemorrhagic infarction in preterm infants: the role of thrombophilia

Periventricular haemorrhagic infarction (PVHI) is a complication of preterm birth associated with cardiorespiratory instability. To date, the role of thrombophilia as a possible additional risk factor in infants with atypical timing and presentation of PVHI has not been investigated. This was a retrospective cohort study of preterm infants who developed PVHI with an atypical timing and presentation either of antenatal onset or late in the postnatal course in the absence of a preceding sudden deterioration of their clinical condition. In infants with atypical PVHI mutation analysis of the factor V Leiden (G1691A), prothrombin (G20210A) gene, and C677T and A1298C polymorphisms in the MTHFR gene was performed, and plasma lipoprotein(a) and homocysteine levels were measured. Sixty-two preterm infants who presented with a PVHI were studied. Seventeen had an atypical presentation (seven males, 10 females; median birthweight 1170g [range 580-1990g]; median gestational age 30.6wks [range 28.7-33.7wks]). The typical PVHI group comprised 28 males and 17 females (median birthweight 1200g [range 670-2210g]; median gestational age 29.6wks [range 25.3-33.6wks]). Among the 17 infants with atypical presentation, the factor V Leiden mutation was found in seven infants (41%) as well as in the mothers of six of these seven infants; in one infant this was concomitant with a prothrombin gene mutation. A polymorphism in the MTHFR gene was also present in these infants. In two infants with an atypical presentation who were tested for this, a mutation in the COL4A1 gene was found (reported previously). All but two of the infants with an atypical presentation developed spastic unilateral cerebral palsy. An atypical presentation of PVHI in preterm infants tends to occur more often in the presence of thrombophilia. Testing of thrombophilia, especially factor V Leiden and prothrombin gene mutation, is recommended in these infants.