Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.5.7.1 (methylenetetrahydrofolate reductase)
2,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inherited thrombophilias--deficiencies of protein C, protein S, and antithrombin III--and the prothrombotic polymorphisms factor V G1691A and factor II G20210A predispose patients toward venous thromboembolism (VTE). The aim of this study was to determine the prevalence of single and combined prothrombotic factors in patients with idiopathic VTE and to estimate the associated risks. The study group consisted of 162 patients referred for work-up of thrombophilia after documented VTE. The controls were 336 consecutively admitted patients. In all subjects factor V G1691A, factor II G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T were analyzed by specific polymerase chain reactions and restriction enzymes. Activities of antithrombin III and protein C, free protein S antigen, and lupus anticoagulant were determined in a subset of 109 patients who were not receiving oral anticoagulants. The prevalences of heterozygotes and homozygotes for factor V G1691A and factor II G20210A among patients and controls were 40.1% versus 3.9% and 18.5% versus 5.4%, respectively (P=0.0001). The prevalence of homozygotes for MTHFR C677T in patients was 22.8% and in controls, 14.3% (P=0.025). Heterozygous and homozygous factor V G1691A, factor II G20210A, and homozygous MTHFR C677T were found to be independent risk factors for VTE, with odds ratios of 16.3, 3.6, and 2.1, respectively. Two or more polymorphisms were detected in 27 of 162 patients (16.7%) and in 3 of 336 controls (0.9%). Logistic regression analysis disclosed odds ratios of 58.6 (confidence interval [CI], 22.1 to 155.2) for joint occurrence of factor V and factor II polymorphisms, of 35.0 (CI, 14.5 to 84.7) for factor V and MTHFR polymorphisms, and of 7.7 (CI, 3.0 to 19.6) for factor II and MTHFR polymorphisms. Among 109 patients in whom a complete thrombophilic work-up was performed, 74% had at least 1 underlying defect. These data indicate that in most patients referred for evaluation of thrombophilia due to idiopathic VTE, 1 or more underlying genetic predispositions were discernible. The presence of >1 of the prothrombotic polymorphisms was associated with a substantial risk of VTE.
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PMID:Single and combined prothrombotic factors in patients with idiopathic venous thromboembolism: prevalence and risk assessment. 1007 51

Terminal limb deficiency defects affect between three and eight babies per 10000 births and are an important cause of disability. Established causes for these malformations include single gene disorders, chromosome abnormalities, teratogens, and amniotic bands. However, the etiology remains unknown in a significant proportion of cases. Several authors have hypothesized that vascular accidents, either bleeds or vessel occlusions, may underlie a substantial number of cases; but, for the most part, the origin of such events remains obscure. Over the past several years, an increasing number of genetic thrombophilias have been recognized and have been associated with increased risks of peri- and post-natal occlusive disease, and with higher rates of recurrent pregnancy loss. The hypothesis to be examined in this pilot study was whether the inherited thrombophilias might be associated with a vascular cause of some terminal limb deficiency defects. Towards that end, protein C, protein S, antithrombin III, factor V Leiden mutation, prothrombin (G20210A) variant, methylenetetrahydrofolate reductase variant, plasma homocysteine, anticardiolipin IgM and IgG antibodies, and lipoprotein (a) were measured in 24 mother-child pairs in which the child had a terminal limb defect. The results provided some evidence that there may be an excess of thrombophilias present in such families and that they may play some etiological role in a subset of these types of limb malformations.
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PMID:A pilot study of the possible role of familial defects in anticoagulation as a cause for terminal limb reduction malformations. 1078 26

Inherited thrombophilia include deficiences of antithrombin III, protein C and protein S, and the factor V Leiden mutation, the prothrombin gene variant, and homozygosity for the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR). The incidence of thromboembolism events during pregnancy and postpartum period among women with thrombophilia is not well known and depends on the prethrombotic state resulting from the interaction of the underlying thrombophilic defect(s), history of congenital thrombophilia, and additional risk factors. In that way, many patients with congenital thrombophilia will require antenatal thromboprophylaxis, the timing of which will depend on the patient's history and thrombophilic disorders. Low molecular weight heparin appeared to be a safe alternative to unfractionated heparin for both the fetus and the mother during the pregnancy. Case-control studies have recently demonstrated that serious obstetrical complications i. e severe preeclampsia, abruptio placentae, intrauterine growth restriction, and stillbirth were frequently associated with inherited thrombophilia. Controlled trials are now urgently needed to determine the possible potential benefits of anticoagulant therapy in pregnancy outcome. Finally, there is no evidence to support routine screening for congenital thrombophilia during pregnancy.
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PMID:[Inherited thrombophilia and pregnancy]. 1080 57

We examined the relationship between placental histology and thrombophilia status in women who were admitted with severe pre-eclampsia/eclampsia, placental abruption, intrauterine growth restriction or unexplained stillbirth. All women had thrombophilia screen at least 10 weeks after delivery (antithrombin III, protein C, protein S, activated protein C resistance, anticardiolipin antibodies, lupus anticoagulant, fasting plasma homocysteine and specific mutations to methylenetetrahydrofolate reductase C677T, G20210A prothrombin gene and factor V Leiden. Placental histology reports were examined to identify the frequency of thrombotic lesions in the placenta including fetal stem vessel thrombosis, fetal thrombotic vasculopathy, placental infarction, perivillous fibrin deposition, intervillous thrombosis and placental floor infarction. During a 17 month period, a cohort of 79 women met the study criteria. Thirty (70%) out of 43 women with abnormal thrombophilia screen had abnormal placental histology. Twenty-eight (78%) out of 36 women with negative thrombophilia screen had abnormal placentae. No specific histological pattern could be identified when thrombophilia positive and thrombophilia negative groups were compared. We propose that there is a poor correlation between thrombophilia status and pathological changes of the placenta in women with severe pregnancy complications.
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PMID:Do placental lesions reflect thrombophilia state in women with adverse pregnancy outcome? 1115 44

The relative risks (odds ratio, OR) of various risk factors for venous thrombophilia, including sex, antithrombin III, protein C (PC), protein S (PS) and plasminogen deficiencies, and C677T homozygous mutation of methylenetetrahydrofolate reductase gene were assessed using age matched (+/-5 years) conditional logistic regression analysis in 116 Chinese venous thrombophilic patients (58 males; 58 females; mean age 47.5+/-17.7 [SD] years) and 125 healthy controls (67 males; 58 females; mean age 45.5+/-15.7 years). None of the patients had prothrombin G20210A and factor V Leiden mutation or an activated PC sensitivity ratio of less than 2. One hundred and five age-matched patients and 105 controls were entered in this analysis. Only PC and PS deficiencies were significantly associated with increased risk for the development of thrombosis with an OR of 10.6 and 6.7, respectively. The findings of this study suggest that PC deficiency and PS deficiency are the most important risk factors for thrombosis in Chinese venous thrombophilic patients.
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PMID:Protein C and protein S deficiencies are the most important risk factors associated with thrombosis in Chinese venous thrombophilic patients in Taiwan. 1097 72

The incomplete penetrance of thrombosis in familial protein C deficiency suggests disease occurs when this deficit is combined with additional abnormalities in the hemostatic system. The pattern of inherited thrombophilia in the Vermont II kindred, which is affected by a clinically dominant type I protein C deficiency, provides strong evidence for a second unidentified gene that segregates independently of protein C deficiency and increases susceptibility to thrombosis. To test the second gene hypothesis, thirty-four candidate genes for proteins involved in hemostasis or inflammation were tested as the unknown defect, using highly polymorphic short tandem repeat (STR) markers in an informative subset (n = 31) of the kindred. The genes considered are; alpha-fibrinogen, beta-fibrinogen, gamma-fibrinogen, prothrombin, tissue factor, factor V, protein S, complement component 4 binding protein, factor XI, factor XII, factor XIIIa, factor XIIIb, histidine rich glycoprotein, high molecular weight kininogen, kallikrein, von Willebrands factor, platelet factor 4, thrombospondin, antithrombin III, alpha-1-antitrypsin, thrombomodulin, plasminogen, tissue plasminogen activator, urokinase plasminogen activator, plasminogen activator inhibitor-1, plasminogen activator inhibitor-2, protein C inhibitor, alpha-2-plasmin inhibitor, kallistatin, lipoprotein a, interleukin 6, interleukin 1, cystathionine-beta-synthase, and methylenetetrahydrofolate reductase. Mutations in many of these genes have been previously established as independent risk factors for thrombosis. However, linkage analysis provided no evidence to implicate any of the candidate genes as the second inherited factor that promotes thrombophilia in this kindred.
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PMID:Genetic screening of candidate genes for a prothrombotic interaction with type I protein C deficiency in a large kindred. 1120 93

Factor V Leiden (FVL) and the prothrombin 20210A (PT-20210A) variant are well-known risk factors for venous thromboembolism (VT). The thermolabile variant (TT) of the methylenetetrahydrofolate reductase (MTHFR) gene, and homozygosity for the 4G allele of the promoter region of the plasminogen activator inhibitor-1 (PAI-1) are potential genetic polymorphisms that have not been consistently associated with increased risk of VT. A case-control study was performed on 192 consecutive unrelated patients referred for evaluation of thrombophilia because of VT and 200 healthy controls. FVL was found in 10.4% of patients compared to 3.0% of controls, while 6.3% of patients were carriers of the PT-20210A allele compared to 2.0% of controls. The adjusted odds ratios (OR) were 5.92 and 4.03 for FVL (P=.001) and the PT-20210A (P=.033), respectively. The prevalence of homozygotes for MTHFR (TT) and PAI-1 (4G/4G) among patients and controls were 13.7% versus 13.0% and 21.6% versus 23.5%, respectively (P=ns). A total of 121 patients underwent a complete screening for FVL, the PT-20210A, protein C (PC), protein S (PS), antithrombin III (ATIII), levels of factor VIII, and antiphospholipid antibodies (aPL). In 59 patients (48.8%) at least one defect was found, being a single defect in 55 and combined defects in 4 patients. Plasma levels of homocysteine (Hcy) were measured in 138 patients and 144 controls. Subjects from both groups carrying the MTHFR-TT variant had higher Hcy levels than those with the normal genotype. Hyperhomocysteinemia (HHcy) by itself is a risk factor for VT (OR 4.92, P<.0001). We conclude that FVL and the PT-20210A are risk factors for VT as well as Hcy levels, but the MTHFR and PAI-1 polymorphisms do not appear to be associated with VT in our country.
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PMID:Major and potential prothrombotic genotypes in a cohort of patients with venous thromboembolism. 1173 73

Mesenteric vein thrombosis (MVT) is uncommon condition. The purpose of this study was to assess prevalence of prothrombotic disorders in these patients. Eleven patients with MVT were screened for protein C, protein S, and antithrombin III deficiencies. Gene analysis was performed by polymerase chain reaction. A prothrombotic disorder was detected in 9 (81.8%) patients. Factor V Leiden, methylenetetrahydrofolate reductase TT677, and prothrombin G20210A mutations were found in 2 (18.2%), 2 (18.2%), and 5 patients (45.4%), respectively. Protein S, protein C, and antithrombin III deficiencies were present in 1, 1, and 2 patients, respectively. Four patients (36.3%) had combined defects. Thus, prothrombotic disorders may have a causative role in the pathogenesis of MVT, and these patients must be screened for these disorders.
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PMID:Prothrombotic disorders in patients with mesenteric vein thrombosis. 1452 88

Our specific aim was to assess associations of thrombophilia, hypofibrinolysis, and polycystic ovary syndrome (PCOS) with recurrent pregnancy loss (RPL) (>/=3 consecutive pregnancy losses < 20 weeks gestation). Prospective studies were performed in 33 Caucasian women referred for diagnosis and treatment of PCOS who were subsequently found to have RPL and in 16 Caucasian women referred for diagnosis and treatment of RPL, who did not have PCOS. Cases (PCOS-RPL, RPL without PCOS) were compared with controls (116 healthy Caucasian females) for the G1691A Factor V Leiden, G20210A prothrombin, C677T methylenetetrahydrofolate reductase (MTHFR), plasminogen activator inhibitor 4G/5G, and platelet glycoprotein PL A1A2 gene mutations. Cases were compared with controls (44 healthy adult Caucasian females) for serologic coagulation tests including homocysteine, proteins C, S, free S, antithrombin III, anticardiolipin antibodies IgG and IgM, dilute Russel's viper venom time, activated partial thromboplastin time, Factor VIII, Factor XI, lipoprotein (Lp)(a), and plasminogen activator inhibitor activity (PAI-Fx). The 33 Caucasian women with PCOS subsequently found to have RPL were 10% of a cohort of 322 Caucasian women who had >/= 1 previous pregnancy and had been referred for diagnosis and therapy of PCOS over a 4.3-year period. The Factor V Leiden G1691 mutation was present in 6 of 33 women (18%) with PCOS-RPL and in 3 of 16 women with RPL without PCOS (19%) versus 2 of 116 (1.7%) female controls, Fisher's P (p(f)) =.0016, p(f) =.013. The 33 PCOS-RPL cases also differed from the 44 female controls for high PAI-Fx (>21.1 U/mL), 38% versus 8%, p(f) =. 004. The thrombophilic G1691A Factor V Leiden mutation is associated with RPL in women with and without PCOS; hypofibrinolysis (high PAI-Fx) is also associated with RPL in women with PCOS.
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PMID:Polycystic ovary syndrome, the G1691A factor V Leiden mutation, and plasminogen activator inhibitor activity: associations with recurrent pregnancy loss. 1466 68

Thromboembolic events during the perinatal period are responsible for irreversible brain damage owing to cerebral hypoxia and neuronal necrosis. We investigated the presence of thrombophilia risk factors in children with congenital neurologic disorders. Nineteen children (9 males and 10 females), aged 1 to 14 years (median 4.5 years), who had presented with symptoms and signs of congenital neurologic disorders were studied. Thirty-five age-matched healthy children recruited from the same geographic area served as controls. Three patients of 19 (15.8%) were carrying the factor V Leiden mutation compared with 2 children among the controls (5.7%). One patient was heterozygous for the prothrombin G20210A variant (5.2%) compared with one child who was heterozygous among the controls. Three patients were homozygous (15.8%) and 11 were heterozygous (57.9%) for the C677T 5,10-methylenetetrahydrofolate reductase gene mutation compared with 4 (11.5%) and 18 (51.4%), respectively, among the controls. Three patients of 19 (15.8%) were carrying more than one mutation. We found 18 mutations in 79% (15/19) of the patients and 25 mutations in 69% (24/35) of the healthy children. Among the individuals carrying the homozygous 677TT 5,10-methylenetetrahydrofolate reductase genotype, we found 7 mutations in 32% (6/19) of the patients and 7 mutations in 20% (7/35) of the healthy children (P > .05). In one patient, lupus anticoagulant and antiphospholipid antibodies of IgG isotype were detected. Reduced activities of protein C, protein S, or antithrombin III were not observed in either the patient or the control group. Although, among our cases, we found some well-known risk factors associated with thrombosis in adults, the pathogenesis of these clinical entities remains obscure.
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PMID:Genetic risk factors associated with thrombosis in children with congenital neurologic disorders. 1599


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