Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Impaired cochlear blood circulation has been suggested to cause sudden hearing loss. In this study, the role of factor V 1691 G-A (FV 1691 G-A), prothrombin 20210 G-A (PT 20210 G-A), methylene tetrahydrofolate reductase 677 C-T (MTHFR 677 C-T), factor V 4070 A-G (FV 4070 A-G), endothelial cell protein C receptor (EPCR) gene 23-bp insertion, and plasminogen activator inhibitor-1 (PAI-1) 4G/5G mutation was assessed. Fifty-three patients with idiopathic sudden sensorineural hearing loss and 80 individuals comprising the control group were included in this study. The frequency for FV 1691 A was 6.2% in the patient group and 3.7% in the control group, PT 20210 G-A was 1.2% in the patient group and 1.9% in the control group, and FV 4070 A-G was 7.5% in the patient group and 11.3% in the control group. The frequency of MTHFR 677 C-T was significantly higher in the patient group than in the control group, with a P value of .03. PAI-1-675 4G/5G polymorphism was found to be 71.2% and 69.8%, in the control group and the patient group, respectively. The EPCR 23-bp insertion was 0% in the control group and was found in 3 patients (3.7%), which needs further study.
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PMID:The importance of thrombotic risk factors in the development of idiopathic sudden hearing loss. 1816 Jun 2

Thalassemia major patients have increased risk for thromboembolic complications because of the chronic hypercoagulable state. The question arising from this is whether thromboembolic complications are the result of genetic polymorphisms of prothrombotic factors. Here, we studied factor V 1691 G-A (FVL), factor II polymorphism (G20210A), methyltetrahydrofolate reductase mutation (MTHFR, C677T), and endothelial cell protein C receptor (EPCR) deletion polymorphism and their relationship with thromboembolic complications. We found significant decrements of protein C and protein S and a slight increased prevalence of congenital thrombophilic mutations when compared with controls. Although 5 of the patients had high soluble EPCR (sEPCR) levels, no significant change was found in sEPCR values between patients and controls.
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PMID:Congenital thrombotic risk factors in beta-thalassemia. 1848 81

Idiopathic portal hypertension (IPH) is characterized by non-cirrhotic presinusoidal intrahepatic portal hypertension. The etiopathogenesis of the disease is poorly understood. Obliteration with microthrombosis of the small portal vein branches may lead to lesions underlying portal hypertension. We aimed to put forward a comprehensive thrombophilic mutation profile in IPH and its probable contribution to pathogenesis. Eleven patients and 12 controls were included. We used the CVD-StripAssay which is based on the reverse-hybridization principle to identify a total of 12 thrombophilic gene mutations: Factor V R506Q, Factor V H1299R, prothrombin G20210A, Factor XIII V34L, beta-Fibrinogen -455 G-A, PAI-1 4G/5G, platelet GPIIIa L33P, MTHFR C677T, MTHFR A1298C, ACE I/D, Apo B R3500Q and Apo E2/E3/E4, respectively. We also evaluated some blood parameters and protein C, protein S, AT-III levels using commercially available assays. IPH patients and controls were similar in respect to gender distribution (P = 1.000). Mean age was 31.2 in patients and 29.1 in controls (P = 0.622). Pica history was present in 54.5% of the patients. Mean protein C and AT-III levels were lower in patients than that of controls (P = 0.002 and 0.001, respectively). Factor XIII V34L, PAI-1, GPIIIa L33P, MTHFR C677T and MTHFR A1298C frequencies of genetic polymorphisms were found to be significantly higher among patients than that of controls. Apolipoprotein E2/E3/E4 analysis showed an inverse relationship with IPH when E2 plus E4 compared with E3. A higher frequency of Beta-Fibrinogen -455G-A mutation was observed in patients, but this difference did not reach a statistical significance. Our data represent the most comprehensive study to date with respect to thrombophilic gene polymorphisms in IPH. The data support a possible pathogenetic role in IPH, at least by some of the prothrombotic mutations. In order to confirm or refuse this proposal, a larger cohort of patients is needed.
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PMID:Analysis of inherited thrombophilic mutations and natural anticoagulant deficiency in patients with idiopathic portal hypertension. 1868 11

The effectiveness of anticoagulant therapy for venous thromboembolism, with regards to both acute phase and long term prophylaxis, in patients with recurrent deep venous thrombosis (DVT) and persistence of risk factors, has been confirmed by many studies. However, it is not free of complications such as hemorrhage or, more rarely, skin necrosis. The patient, observed by us since 1994, was treated with oral vitamin K antagonists: he was affected by post-thrombotic syndrome and deficiency of congenital procoagulant factors (factor II heterozygote and MTHFR positive heterozygote) and secondary deficiency of procoagulant factors due to the consumption of protein C, with appearance of skin necrosis that occurred after many years of oral anticoagulant treatment. The change of therapy from oral anticoagulant to low molecular weight heparin and the use of local dressing, led to the resolution of the clinical symptoms and on to healing.
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PMID:Skin necrosis during oral anticoagulant long-term treatment: an atypical side. 1919 May 62

Molecular genetic methods passed into the field of investigation of thrombophilic states in 90th years of last century, along with the first discoveries of coagulation inhibitors (AT III, protein C and protein S). They have acquired a widespread use above all with the detection of the molecular basis of activated protein C (APC) resistance in 1994 by prof. Bertina. At the present time, a wide range of molecular genetic markers, linked with a clearly documented increased risk of thrombophilia are adapted. They include mutations of factor V Leiden 506R/Q, of protrombin 20210G/A, MTHFR 677C/T in homozygous form, mutation of PAI-1 4G/5G, mutations of different coagulation inhibitors and finally a range of polymorphisms with still not precisely defined increased risk for thrombophilia (F XIII Val34leu, platelets glycopeproteins, endothelial protein C receptor and trombomodulin). From the methodological viewpoint, all these techniques are based on the principle polymerase chain reaction (PCR). In the last period of time, however there was a rapid evolution, allowing a significant improvement in their laboriousness. Nowadays, splitting with the aid of restriction endonucleases, real time PCR or allel specific primers for PCR. The second, where molecular genetic methods are currently under use, is pathophysiological investigation of the single coagulation processes. Here, in a fact, most significant progress has been in the field of APC resistance made elucidation. Although still in the 90th years of the past century the genetical cause of these coagulation disturbance was unequivocally documented its clinically heterozygous appears not yet fully understood at the moment. Similarly, in prothrombin mutation, only the latest investigations have outlined the probable mechanism of expression. Concerning the future evolution of molecular genetic methods, there can be observed a clear cut tendency to better understanding the pathophysiologic cause of thrombophilia in comparison with the searching for new coagulation defects which consecutively bear lesser a relative risk of thrombosis.
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PMID:[Molecular methods in thrombophilic states diagnostics]. 1937 63

Recurrent fetal loss (RFL) is a significant clinical problem, occurring in 1% to 5% of reproductive females. Inherited or acquired thrombophilia has been diagnosed in 50% to 65% of women with history of unexplained fetal loss. The objective of our study was to determine the prevalence of thrombophilia in women with unexplained RFL in Serbian population and to find out whether the presence of thrombophilia is associated with pregnancy losses that occur later than 12th gestational week. We have examined 147 women with unexplained RFL or intrauterine fetal death and 128 healthy women with at least 1 uncomplicated pregnancy. The antithrombin (AT), protein C (PC), protein S (PS), activated protein C (APC) resistance, factor V (FV) G1691A, factor II (FII) G20210A, and MTHFR C677T were determined. At least 1 inherited thrombophilic defect was found in 54 (36.7%) of 147 women with repeated fetal losses and in 11 (8.59%) of 128 controls (P < .001, OR 6.17, 95% CI 3.06-12.48). The most common thrombophilic abnormalities were homozygosity for MTHFR 677TT, FV Leiden, and FII G20210A. Deficiency of natural anticoagulants occurred in 10 patients, with protein S deficiency being the most frequent one. Thrombophilia was found in 46 of 94 women with RFL that occurred later than the 12th gestational week and in only 8 of 53 with RPL earlier than 12th week (P = .001). Our study has shown the association between the hereditary thrombophilia and RFL that occurred after the 12th gestational week in Serbian population.
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PMID:Inherited thrombophilia is associated with pregnancy losses that occur after 12th gestational week in Serbian population. 1952 Jun 81

Isolated renal vein thrombosis is very rare without the presence of nephrotic syndrome. It is more common in the newborns and infants. Whereas major risk factors in adults are the procoagulant states such as protein C or S deficiency, factor V Leiden mutation, primary or secondary antiphospholipid syndrome, severe hypothyroidism, and trauma. Here, we report a case of isolated renal vein thrombosis associated with MTHFR-1298 and PAI-1 4G gene mutations. It should be noted that the presence of MTHFR-1298 and PAI-1 4G gene mutations together might be one of the examples of genetic mutation combinations that increase the likelihood of a thrombotic event.
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PMID:Isolated renal vein thrombosis associated with MTHFR-1298 and PAI-1 4G gene mutations. 1982 18

Interrelationships between genetic and biochemical factors underlying ischemic stroke and ischemic heart disease are poorly understood. We: 1) undertook the most comprehensive meta-analysis of genetic polymorphisms in ischemic stroke to date; 2) compared genetic determinants of ischemic stroke with those of ischemic heart disease, and 3) compared effect sizes of gene-stroke associations with those predicted from independent biochemical data using a mendelian randomization strategy. Electronic databases were searched up to January 2009. We identified: 1) 187 ischemic stroke studies (37,481 cases; 95,322 controls) interrogating 43 polymorphisms in 29 genes; 2) 13 meta-analyses testing equivalent polymorphisms in ischemic heart disease; and 3) for the top five gene-stroke associations, 146 studies (65,703 subjects) describing equivalent gene-biochemical relationships, and 28 studies (46,928 subjects) describing biochemical-stroke relationships. Meta-analyses demonstrated positive associations with ischemic stroke for factor V Leiden Gln506, ACE I/D, MTHFR C677T, prothrombin G20210A, PAI-1 5G allele and glycoprotein IIIa Leu33Pro polymorphisms (ORs: 1.11 - 1.60). Most genetic associations show congruent levels of risk comparing ischemic stroke with ischemic heart disease, but three genes--glycoprotein IIIa, PAI-1 and angiotensinogen--show significant dissociations. The magnitudes of stroke risk observed for factor V Leiden, ACE, MTHFR and prothrombin, but not PAI-1, polymorphisms, are consistent with risks associated with equivalent changes in activated protein C resistance, ACE activity, homocysteine, prothrombin, and PAI-1 levels, respectively. Our results demonstrate causal relationships for four of the most robust genes associated with stroke while also showing that PAI-1 4G/5G polymorphism influences cardiovascular risk via a mechanism not simply related to plasma levels of PAI-1 (or tPA) alone.
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PMID:Causal relationship of susceptibility genes to ischemic stroke: comparison to ischemic heart disease and biochemical determinants. 2016 34

Thirty-six patients with stroke, aged from 8 months to 15 years, and 28 control children, aged 1-15 years, were studied. In both groups, the evaluation of anamnesis, neurologic status and genotyping for 11 most common prothrombotic polymorphisms were carried out. Coagulogram tests and measurement of homocysteine were performed before the anticoagulant therapy in the main group. The total frequency of prothrombin gene mutations (G20210A, factor V Leiden, MTHFR C677T and MTRR A66G) was 2.8 times higher in the main group compared to the control one. The most frequent genotypes were 677TT (8.3% of cases) and 66GG (30.6%). In patients with stroke, the homocysteine level exceeded the upper limit of normal age and also was significantly elevated in carriers of abovementioned risk genotypes: 10.29 +/- 1.55 mcmol/l vs 7.33 +/- 0.6 mcmol/l (p = 0.018). The coagulogram revealed disorders of anticoagulant system, including the decrease of protein C activity (22.7% of cases), protein S activity (13.6%) and antithrombin III (12.5%) and the increase of D-dimer level (21% of cases). It has been suggested to screen for common prothrombotic states and measure homocysteine levels in children with ischemic stroke and to lower homocysteine levels by using vitamins B6 and B12' and diet.
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PMID:[Prothrombotic disturbances in children after ischemic stroke]. 2087 2

Inherited thrombophilia may cause important complications in pregnancies including maternal death, early and late pregnancy loss, preeclampsia, intrauterine growth restriction and placental abruption. This study was developed to investigate the fetal loss and successful birth rates in hereditary thrombophilic patients treated with low-dose acetylsalicylic acid and low molecular weight heparin to determine the necessity and effectiveness of this treatment. Ninety-three patients with the history of recurrent pregnancy loss or thromboembolism were included in this study. Eighty milligram acetylsalicylic acid treatment was started just after the diagnosis for the patients with hereditary thrombophilia, continued throughout pregnancy and ceased 3 days before the delivery. Low molecular weight heparin (LMWH) was started for the patients with the unsuccessful in-vitro fertilization (IVF) history, just after finishing the egg collection. For the other patients, LMWH was started after the positive result of the pregnancy test. Treatment was started for 67 (72%) of patients. Among the treated 67 patients, 38 had MTHFR C677T gene mutation, 25 had protein S deficiency, 19 had FV Leiden mutation, four had protein C deficiency, two had Prothrombin 20210A gene abnormality, two had antiphospholipid anticore syndrome and two had AT III deficiency. Fifty-seven (85.1%) of 67 patients under treatment had pregnancy. Forty-one (61.2%) of those 57 patients had a live birth, whereas 16 (23.9%) of them had abortus under treatment. In regression analysis, only protein C and S deficiencies were found to be independent risk factors. In conclusion, inherited thrombophilia should always be kept in mind as an etiological factor of recurrent abortus. With treatment, success rates are between 60 and 80%. Severe side effects due to treatment are rare. But randomized, double-blind, placebo-controlled studies are still necessary to evaluate the benefit of heparin and acetylsalicylic acid treatment in women with the history of inherited thrombophilia.
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PMID:Treatment of adverse perinatal outcome in inherited thrombophilias: a clinical study. 2104 5


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