Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Catastrophic antiphospholipid syndrome (CAPS) is a severe and rare variant of antiphospholipid syndrome (APS) characterized by acute multiorgan failure due to small vessel thrombi in patients with positive antiphospholipid antibodies. We report a fatal case of catastrophic antiphospholipid syndrome in a young woman with a history of polymyositis and Hodgkin lymphoma. The patient was admitted to hospital because of severe foot pain following several weeks of skin ulcerations. Doppler ultrasonography showed evidence of arterial ischemia of the both lower extremities. Despite anticoagulation, immunosuppression, plasmapheresis and antibiotic therapy, she developed cutaneous gangrene, retroperitoneal hematoma, ileus, and acute respiratory and renal failure that resulted in death. Autopsy showed multifocal vascular injury and microthrombi with associated hemorrhages and infarcts in multiple organs. The patient had normal levels of functional protein C and protein S and a normal level of plasma homocysteine. Tests for common thromophilic gene mutations including prothrombin 20210, factor V Leiden 1691, and methylene tetrahydrofolate reductase 677 were negative. To our knowledge, this is the first CAPS patient with molecular studies for genetic prothrombotic mutations. Our report showed that there was no association between the development of CAPS and inherited thromophilia.
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PMID:Catastrophic antiphospholipid syndrome: a rare cause of disseminated microvascular thrombotic injury - a case report with pathological and molecular correlative studies. 1574 23

In this study, we investigated some of the prothrombothic mutations and polymorphisms in 15 children with congenital cardiac malformations who developed severe thrombosis in the perioperative period following surgical repair. The mutations and polymorphisms included in the study were Factor V Leiden, prothrombin G20210A, methylentetrahydrofolate reductase C677T, endothelial nitric oxide synthase intron 4 VNTR, alpha-fibrinogen Thr312Ala, Factor XIII Val34Leu, and insertion or deletion of angiotensin 1 converting enzyme. Compared to the healthy Turkish subjects, our patients had a similar rate of mutation of Factor V Leiden, Factor XIII Val34Leu, and endothelial nitric oxide synthase a/b polymorphisms, but higher frequency of the prothrombotic angiotensin 1 converting enzyme deletion/deletion genotype, and lower frequency of the antithrombotic alpha fibrinogen Thr/Thr genotype. None of the patients exhibited mutations involving prothrombin G20210A or methylentetrahydrofolate reductase C677T. The results of our study suggest that, in addition to prothrombotic mutations such as Factor V Leiden, single-nucleotide polymorphisms should be considered in all children with congenital cardiac malformations who develop thrombosis. Malformations of the heart are the most common of all serious lesions that are present at birth, with an incidence of 4 to 8 cases per 1,000 live births. If needed, corrective surgery is usually the optimal treatment for these anomalies, but perioperative morbidity and mortality still remain high due to several factors. Arterial or venous thrombosis, or both varieties of thrombosis, is among these factors. Prior to surgery, the most frequent time at which these children develop thrombosis is during cardiac catheterization. Postoperative thrombosis in this group of patients is a more complex disorder, which can affect both small and large vessels, and is associated with a high morbidity and mortality. Recent studies indicate that both point mutations and single-nucleotide polymorphisms of genes that encode proteins involved in the coagulative and anticoagulative cascades are important risk factors for development of thrombosis. Patients with these risk factors are most likely to develop thrombosis when triggering elements, such as placement of catheters, prolonged immobilization, or surgery, are also present. In this study, we investigated some of the above-mentioned mutations and polymorphisms in children who developed thrombosis in the perioperative period after correction of congenital cardiac malformations.
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PMID:Analysis of prothrombotic mutations and polymorphisms in children who developed thrombosis in the perioperative period of congenital cardiac surgery. 1583 Nov 56

Hereditary risk determinants of venous thrombosis have been reported to be associated with severe preeclampsia. So far there are no data to support whether these risk determinants are related to the time of onset of severe preeclampsia. We used a case-control design, studying 97 women with severe preeclampsia in previous pregnancies and 277 normal women, to assess hereditary risk factors of venous thrombosis as risk determinants for severe preeclampsia. A case-only design comprising solely the 97 women with a history of preeclampsia was used to evaluate these risk factors as risk determinants for early onset of severe preeclampsia. Using the case-control design, there was no significant risk association of the hereditary risk factors with severe preeclampsia [factor V Leiden, odds ratio (OR) 0.9, 95% confidence interval (CI) 0.4, 2.2; prothrombin mutation, OR 1.9, 95% CI 0.5, 7.0; methylentetrahydrofolate reductase 677TT genotype, OR 0.8, 95% CI 0.4, 1.8; plasminogen activator inhibitor (PAI-1) 4G/4G genotype, OR 1.2, 95% CI 0.7, 2.1; PAI-1 5G/5G genotype, OR 1.0, 95% CI 0.5, 1.8]. However, the onset of severe preeclampsia was significantly earlier in women with the G20210A prothrombin gene mutation (24.5 weeks vs. 30.1 weeks, P = 0.046) and in women with the PAI-1 5G/5G genotype (25.7 weeks vs. 30.8 weeks, P = 0.024). Hereditary risk factors for venous thrombosis do not predispose for severe preeclampsia. However, women who are carriers of the G20210A prothrombin gene mutation and the PAI-1 5G/5G genotype are at risk for early onset of severe preeclampsia. It appears that these risk factors do not induce the pathomechanism but accelerate the course of preeclampsia.
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PMID:The G20210A prothrombin-gene mutation and the plasminogen activator inhibitor (PAI-1) 5G/5G genotype are associated with early onset of severe preeclampsia. 1584 53

Simvastatin, a widely used 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, effectively reduced cardiac death and ischemic events in patients with coronary heart disease (CHD) and diabetes mellitus (DM). The mechanism of cardiovascular benefits of statins in DM remains unclear. We examined how simvastatin influences the levels of several in vivo markers for coagulation and fibrinolysis in 26 Type 2 DM patients. The diabetic patients received 20 mg/day of simvastatin up to 12 months. The levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-c) and triglycerides in peripheral circulation of patients were significantly reduced after > or =6 weeks of simvastatin treatment. Levels of prothrombin fragment 1+2 (F1+2), factor VII, plasminogen activator inhibitor-1 (PAI-1) and tissue factor pathway inhibitor (TFPI) antigens, but not tissue plasminogen activator (tPA) antigen, in the pre-simvastatin plasmas of the diabetic patients were significantly higher than the levels found in plasmas of healthy subjects. Significant reductions in F1+2 and PAI-1 levels were evident > or =6 weeks after the diabetic patients received simvastatin. Levels of total tPA, TFPI, FVII, hemoglobin A1c, fasting blood glucose, and insulin in the diabetic patients' plasma were not significantly altered by simvastatin treatment. Positive correlations were found between PAI-1 versus TC, PAI-1 versus LDL-c, and FVII versus triglycerides in the plasmas of simvastatin-treated patients. The results suggest that simvastatin reduces in vivo prothrombinase activity and PAI-1 levels in type 2 DM patients. These actions may contribute to the protective properties of simvastatin against ischemic events in diabetic patients.
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PMID:Impact of simvastatin on hemostatic and fibrinolytic regulators in Type 2 diabetes mellitus. 1618 73

Pregnancy is a well recognized thrombophilic risk factor. Recurrent abortion (RA) affect up to 3% of fertile couples. A 50% of these cases are considered as idiopathic. Some of them may have one or more than one thrombophilic alterations. RA may be related to placental flow abnormalities. Up to 1% to 5% of all pregnancies may be complicated with placental flow abnormalities. Antiphospholipid syndrome, PS, PC, ATIII deficiencies, factor V, prothrombin, methylentetrahydrofolate reductase, plasminogen activator inhibitor type 1, fibrinogen and factor XIII polymorphisms, have been strongly related to bad obstetric outcomes, specially RA. The presence of more than one thrombophilic factor may be present in pregnant women, rising the risk of suffering RA. All pregnant patients and those who planed a future conception having a history of thrombotic events, independently of their previous obstetric outcomes, need to be studied for thrombophilia. All patients with RA specially if it appeared in the late-pregnancy, have also to be studied. Early antiaggregant and/or anticoagulant therapy, reduces the maternal-fetal risk.
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PMID:[Recurrent miscarriage and inherited thrombophilia: diagnostic work-out and therapeutic management]. 1628 74

A new modification of the single nucleotide polymorphism (SNP) analysis (DSNP, duplex-specific nuclease preference) method using the duplex-specific nuclease from the king crab was proposed. The method was used to study SNPs in the following human genes: kRAS, nRAS, hRAS, and p53, the genes of blood coagulation factor V, methyltetrahydrofolate reductase, prothrombin, and apolipoprotein E and a deletion in the BRCA1 gene. DSNP was shown to be useful for the estimation of the mutant allele content in DNA samples. A system for the simultaneous identification of several adjacent single-nucleotide polymorphisms in the kRAS gene was proposed. The approaches could be used to develop test systems for the detection of SNPs in human genes. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 6; see also http://www.maik.ru.
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PMID:[Application of the duplex-specific nuclease preference method to the analysis of point mutations in human genes]. 1636 36

This review summarizes recent information about the major thrombophilic conditions, their clinical relevance, and practical aspects pertaining to testing for these thrombophilias, such as when to test and what assays are appropriate. Conditions covered include factor V Leiden, prothrombin 20210 mutation, proteins C and S, antithrombin, antiphospholipid antibodies, homocysteine, and methylene-tetrahydrofolate-reductase enzyme mutation. Additional comments focus on education of patients and educational resources for patients, such as the National Alliance for Thrombosis and Thrombophilia (www.nattinfo.org).
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PMID:Thrombophilias--practical implications and testing caveats. 1647 36

Anticoagulant pesticides are used widely in agricultural and urban rodent control. The emergence of warfarin-resistant strains of rats led to the introduction of a new group of anticoagulant rodenticides variously referred to as 'superwarfarins', 'single dose' or 'long-acting'. This group includes the second generation 4-hydroxycoumarins brodifacoum, bromadiolone, difenacoum, flocoumafen and the indanedione derivatives chlorophacinone and diphacinone. Most cases of anticoagulant rodenticide exposure involve young children and, as a consequence, the amounts ingested are almost invariably small. In contrast, intentional ingestion of large quantities of long-acting anticoagulant rodenticides may cause anticoagulation for several weeks or months. Occupational exposure has also been reported. Anticoagulant rodenticides inhibit vitamin K(1)-2,3 epoxide reductase and thus the synthesis of vitamin K and subsequently clotting factors II, VII, IX and X. The greater potency and duration of action of long-acting anticoagulant rodenticides is attributed to their: (i) greater affinity for vitamin K(1)-2,3-epoxide reductase; (ii) ability to disrupt the vitamin K(1)-epoxide cycle at more than one point; (iii) hepatic accumulation; and (iv) unusually long biological half-lives due to high lipid solubility and enterohepatic circulation. Substantial ingestion produces epistaxis, gingival bleeding, widespread bruising, haematomas, haematuria with flank pain, menorrhagia, gastrointestinal bleeding, rectal bleeding and haemorrhage into any internal organ; anaemia may result. Spontaneous haemoperitoneum has been described. Severe blood loss may result in hypovolaemic shock, coma and death. The first clinical signs of bleeding may be delayed and patients may remain anticoagulated for several days (warfarin) or days, weeks or months (long-acting anticoagulants) after ingestion of large amounts. There are now sufficient data in young children exposed to anticoagulant rodenticides to conclude that routine measurement of the international normalised ratio (INR) is unnecessary. In all other cases, the INR should be measured 36-48 hours post exposure. If the INR is normal at this time, even in the case of long-acting formulations, no further action is required. If active bleeding occurs, prothrombin complex concentrate (which contains factors II, VII, IX and X) 50 units/kg, or recombinant activated factor VII 1.2-4.8 mg or fresh frozen plasma 15 mL/kg (if no concentrate is available) and phytomenadione 10mg intravenously (100 microg/kg bodyweight for a child) should be given. If there is no active bleeding and the INR is < or =4.0, no treatment is required; if the INR is > or =4.0 phytomenadione 10mg should be administered intravenously.
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PMID:Anticoagulant rodenticides. 1649 7

The impact of the G20210A prothrombin mutation, factor V Leiden and 677T mutation of methylene tetrahydrofalate reductase (MTHFR) in recurrent deep venous thrombosis (DVT) is not so clear. We have prospectively monitored 259 patients following a first episode of DVT in order to determine which factors influence the development of a recurrent event. Several clinical and biological factors together with the genetic polymorphisms of factor V Leiden, G20210A prothrombin and 677T MTHFR were assessed. During a median follow-up of 786 patient-years, 27 patients (14%) developed one objective episode of recurrent venous thrombosis. The carriers of a double defect, homozygous or double heterozygous for factor V Leiden and G20210A, had an increased risk after a first episode of DVT, while patients who were isolated heterozygous for factor V Leiden or G20210 had a risk of recurrent DVT similar to patients who had neither mutation (annual incidence of 12.1, 3.1, 2.9 and 2.8%). The 677T MTHFR mutation alone or combined with hyperhomocysteinemia was not associated with an increased risk of recurrent events. The development of proximal DVT (P=0.01) and the presence of a double defect (P=0.01) were the only two risk factors independently associated with a high recurrence ratio in the multivariate analysis. Thus, the annual incidence of DVT recurrence in patients without any of these two risk factors was only 0.6% (95% confidence interval, 0.2-0.9). We have identified a group of patients with DVT but at very low risk of re-thrombosis in whom an extended secondary thromboprophylaxis should be carefully considered.
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PMID:Risk of recurrent venous thrombosis in patients with G20210A mutation in the prothrombin gene or factor V Leiden mutation. 1660 75

There are significant differences among patients treated with warfarin in the dosage volumes necessary to reach an optimum therapeutic effect. Apart from the external influences (interactions with drugs and food), genetic predispositions play an important role. Polymorphysms of the P 450 2C9 cytochrome bear upon the speed ofbreaking down S-warfarin, polymorfysms VKORC1 bear on the volume and quality of epoxide reductase--an enzyme whose blockade is the crux of the mechanism how cumarin anticoagulants act. These two genes are responsible for at least 50% of the warfarin effect variability. Warfarin's effect is further determined by the genetic variants of gamma-carboxylase, prothrombin, factors VII and IX. In near future, further results of pharmacogenetic research and clinical studies can be expected. They study the impact of the findings in clinical practice.
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PMID:[Pharmacogenetics of warfarin]. 1663 47


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