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)

To elucidate the roles of the ABO blood group, von Willebrand factor (vWF), and clotting factor VIII in the process of deep-vein thrombosis we undertook a population-based patient-control study in which 301 consecutive patients younger than 70 with a first, objectively diagnosed episode of venous thrombosis and without an underlying malignant disorder were compared with 301 healthy controls matched for age and sex. In univariate analysis, blood group, vWF concentration, and factor VIII concentrations were all related to deep-vein thrombosis. The risk of thrombosis increased with increasing vWF or factor VIII concentration and was higher in subjects of non-O blood groups than in those of group O. In multivariate analysis only factor VIII remained as a risk factor, and the dose-response relation between factor VIII concentration and risk of thrombosis persisted (subjects with factor VIII concentrations above 1500 IU/L had an adjusted odds ratio of 4.8 [95% Cl 2.3-10.0]). By contrast, the adjusted odds ratio for each vWF stratum did not differ from 1, and that for blood group was 1.5 (1.0-2.2). Our findings point to an effect on thrombosis risk of vWF and blood group, the former fully and the latter at least partly mediated through factor VIII. The 25% prevalence of factor VIII concentrations above 1500 IU/L among unselected consecutive thrombosis patients and the high adjusted relative risk for thrombosis lead to the conclusion that high factor VIII concentrations are common and represent a clear increase in risk of thrombosis, similar to the risks conferred by deficiencies of the coagulation-inhibiting proteins and activated protein C resistance.
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PMID:Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. 789 20

Resistance to activated protein C (APC) has been recently identified as a common abnormality of the clotting system that significantly increases the risk of venous thromboembolism. The distribution of plasma response to APC in the general population and the variables potentially influencing it are however unknown. In this study, we analyzed the data from the first 4,000 subjects enrolled in the Vicenza Thrombophilia and Atherosclerosis (VITA) Project to identify the demographic and laboratory variables affecting the plasma response to APC. Plasma response to APC, expressed as APC-ratio, was significantly influenced not only by the presence of the FV Leiden mutation but also by the aPTT ratio, triglycerides, fibrinogen and cholesterol level and by pill use, ABO blood group, gender, smoke, body-mass index and age. The effect of these variables was independent of the presence of the FV Leiden mutation, and adjustment for their effect improved the discriminating efficiency of the APC-ratio for the presence of the FV Leiden mutation. Notwithstanding adjustment, the APC ratio was unsuitable for screening purposes in the general population (positive predictive value 82.7%).
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PMID:The VITA project: phenotypic resistance to activated protein C and FV Leiden mutation in the general population. Vicenza Thrombophilia and Atherosclerosis. 926 85

Limited data exist on the impact of additional genetic risk factors on the clinical manifestations of factor (F) V Leiden homozygotes. A retrospective multi-centre cohort study was performed to assess the role of the FII G20210A gene mutation, the protein C (PC) promoter CG haplotype, the combination of two PC polymorphisms (A-1641G, C-1654T), the FXIII Val34Leu polymorphism, two thrombin-activatable fibrinolysis inhibitor polymorphisms (Thr325Ile, Ala147Thr), two plasminogen activator inhibitor-1 polymorphisms (-675 4G/5G, A-844G), the methylene-tetrahydrofolate reductase (MTHFR) C677T polymorphism and the ABO blood group on the thrombotic phenotype in FV Leiden homozygotes. 127 subjects with venous thrombosis and 53 asymptomatic subjects were analysed. The T allele of MTHFR C677T was more frequent in symptomatic subjects than in asymptomatic ones (68% vs. 45%, P = 0.02; odds ratio (OR) 2.8, 95% CI 1.3-5.8, after adjustment for potential confounders). For the other polymorphisms, no difference was observed between symptomatic and asymptomatic subjects. The non-O blood group was more frequent among symptomatic carriers (84% vs. 57%, P = 0.0002; OR 4.1, 95% CI 1.7-9.7). In conclusion, except for the ABO blood group, none of the polymorphisms studied contribute strongly to the thrombotic risk in FV Leiden homozygotes.
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PMID:ABO blood group but not haemostasis genetic polymorphisms significantly influence thrombotic risk: a study of 180 homozygotes for the Factor V Leiden mutation. 1710 52

Most cases of a predisposition to venous thrombosis are caused by resistance to activated protein C, associated in 95% of cases with the Factor V Leiden allele (FVL or R506Q). Several recent studies report a further increased risk of thrombosis by an association between the AB alleles of the ABO blood group and Factor V Leiden. The present study investigated this association with deep vein thrombosis (DVT) in individuals treated at the Hemocentro de Pernambuco in northeastern Brazil. A case-control comparison showed a significant risk of thrombosis in the presence of Factor V Leiden (OR = 10.1), which was approximately doubled when the AB alleles of the ABO blood group were present as well (OR = 22.3). These results confirm that the increased risk of deep vein thrombosis in the combined presence of AB alleles and Factor V Leiden is also applicable to the Brazilian population suggesting that ABO blood group typing should be routinely added to FVL in studies involving thrombosis.
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PMID:Increased risk of venous thrombosis by AB alleles of the ABO blood group and Factor V Leiden in a Brazilian population. 2163 78

Thromboembolism (TE) is a complex disease caused by various acquired and inherited factors. The common mutations; factor V Leiden G1691A (FVL G1691A), prothrombin G20210A (PTG20210A), and methylene tetrahydrofolate reductase C677T (MTHFR C677T) are important inherited causes in both venous and arterial thrombosis. The association between ABO blood groups and thrombophilia has been noted by researchers. We aimed to determine the frequency and association of ABO blood groups as a risk factor along with 3 thrombophilia mutations and another 3 thrombophilia markers in a group of patients with unstimulated thrombosis. In a prospective case-control study, we focused on 100 samples, 50 patients with documented thrombosis as well as 50 healthy age-matched controls. Multiplex polymerase chain reaction and reverse hybridization to oligonucleotide particular probes were employed to detect FVL G1691A, PT G20210A, and MTHFR C677T mutations. Analysis of other thrombophilia markers including protein C (PC), protein S (PS), and antithrombin (AT) assays was also performed. ABO blood group typing was done according to standard methods. Non-O blood group was significantly more frequent among cases than controls (76% vs 54%) with high odds of TE (odds ratio [OR] = 2.69). Positivity for at least 1 thrombophilia marker was more in cases (60%) than controls (34%; OR = 2.9). The combined effect of non-O blood group and thrombophilia markers raised the risk of TE (OR = 4.16, P = .001), particularly FVL (OR = 6.76). This study illustrates that harboring the non-O blood group poses an additive effect with other thrombophilia markers in the causation of TE.
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PMID:ABO Blood Groups and Thrombophilia Markers in Patients With Unstimulated Thrombosis in Kurdistan Region of Iraq. 3237 94

Saudi women have recently started using oral contraceptives (OCs), which has led to risk of venous thromboembolism (VTE). The risk varies with the type of OC generations used, and with OC use the risk for VTE increases by 2- to 6-fold. This study evaluated the effect of OC types in relation to ABO blood group on the risk of VTE among Saudi women. Thrombin generation (TG) was measured in the plasma of the women in the presence and absence of platelet rich plasma, platelet poor plasma and thrombomodulin or activated protein C. OC usage increased TG parameters ETP and Peak height by 9.81% and 16.04%, respectively. An increased risk of VTE was seen among women on third generation OCs as compared to those on second generation products. Within OC generations, we found that for women using fourth generation OCs, their ETP increased by 36.18% as compared to those using second generation and by 6.07% in those using third generation compared to those using second generation. There was significant difference with respect to ABO blood groups and OC generation types, but larger sample size is required. Women who are 40 years and older and using third generation OC had a higher risk of having thrombosis (11.84%), as compared to those using second generation OC (8.79%) and to those using fourth generation OC (5.03%). An association between different OC groups and non-O blood group in thrombosis generation was noted. TG parameters were significantly increased in relation to BMI when comparing to OC users versus non-users. In addition, inhibition of TG parameters in the presence of recombinant human thrombomodulin (TM) and activated protein C (APC) were significantly increased.
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PMID:Oral Contraceptive Types in Relation to ABO Blood Groups Among Saudi Women of Different Reproductive Age Groups and Impact on Venous Thromboembolism. 3311 84