CMRES
MCID: CMR002
MIFTS: 56

Coumarin Resistance (CMRES)

Categories: Blood diseases, Cardiovascular diseases, Genetic diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Coumarin Resistance

MalaCards integrated aliases for Coumarin Resistance:

Name: Coumarin Resistance 56 25 73 36 13 71
Warfarin Resistance 56 12 52 25 73 54
Warfarin Sensitivity 56 12 52 25 71
Warfarin Response 25 29 6
Poor Metabolism of Coumarin 25 73
Coumadin Sensitivity 52 25
Coumarin, Poor Metabolism of 56
Drug Resistance 43
Cmres 73

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant


HPO:

31
coumarin resistance:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0080665 DOID:0080666
OMIM 56 122700
KEGG 36 H01205
MeSH 43 D004351
SNOMED-CT via HPO 68 191124002 263681008 34093004
UMLS 71 C0750384 C2608079

Summaries for Coumarin Resistance

Genetics Home Reference : 25 Warfarin resistance is a condition in which individuals have a high tolerance for the drug warfarin. Warfarin is an anticoagulant, which means that it thins the blood, preventing blood clots from forming. Warfarin is often prescribed to prevent blood clots in people with heart valve disease who have replacement heart valves, people with an irregular heart beat (atrial fibrillation), or those with a history of heart attack, stroke, or a prior blood clot in the deep veins of the arms or legs (deep vein thrombosis). There are two types of warfarin resistance: incomplete and complete. Those with incomplete warfarin resistance can achieve the benefits of warfarin treatment with a high dose of warfarin. Individuals with complete warfarin resistance do not respond to warfarin treatment, no matter how high the dose. If people with warfarin resistance require anticoagulant therapy and take the average warfarin dose, they will remain at risk of developing a potentially harmful blood clot. Both types of warfarin resistance are related to how the body processes warfarin. In some people with warfarin resistance, their blood-clotting process does not react effectively to the drug. Others rapidly break down (metabolize) warfarin, so the medication is quickly processed by their bodies; these individuals are classified as "fast metabolizers" or "rapid metabolizers" of warfarin. The severity of these abnormal processes determines whether the warfarin resistance is complete or incomplete. Warfarin resistance does not appear to cause any health problems other than those associated with warfarin drug treatment.

MalaCards based summary : Coumarin Resistance, also known as warfarin resistance, is related to vitamin k deficiency bleeding and thrombosis. An important gene associated with Coumarin Resistance is VKORC1 (Vitamin K Epoxide Reductase Complex Subunit 1), and among its related pathways/superpathways are Drug metabolism - cytochrome P450 and Linoleic acid metabolism. The drugs Iron and Rilpivirine have been mentioned in the context of this disorder. Affiliated tissues include lung, breast and testes, and related phenotypes are abnormality of metabolism/homeostasis and abnormality of blood and blood-forming tissues

Disease Ontology : 12 An inherited metabolic disorder that is characterized by a high tolerance for the drug warfarin.

NIH Rare Diseases : 52 Warfarin resistance is a condition that is characterized by a high tolerance for a "blood-thinning" medication called warfarin . Warfarin is an anticoagulant that is often prescribed to people who are at an increased risk for blood clots . Some people with a warfarin resistance do not respond to the drug at all, while others can achieve the benefits of warfarin treatment at a high dose. In either case, affected people will still be at an elevated risk for blood clots when given the standard dose of warfarin. The metabolism of warfarin and the drug's effects in the body are complex traits that are determined by several genes as well as environmental and lifestyle factors such as gender, age, weight, diet, and other medications. One specific genetic polymorphism in the VKORC1 gene accounts for approximately 20% of variation in the response to warfarin and can be passed on to future generations in an autosomal dominant manner.

OMIM : 56 Warfarin is a widely prescribed anticoagulant for the prevention of thromboembolic diseases for subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement (Yuan et al., 2005). The dose requirement is highly variable, both interindividually and interethnically. Variation in the VKORC1 gene is believed to be the most important individual predictor of warfarin dose, accounting for about 30% of the variance observed in dosing (Ross et al., 2010). (122700)

KEGG : 36 Warfarin is widely prescribed anticoagulant for the prevention of thromboembolic diseases. However, its use is made difficult by the wide interindividual variation in dose required to achieve a therapeutic effect, the narrow therapeutic range, and the risk of serious bleeding. Warfarin dose requirement is influenced by factors such as intake of vitamin K, ethnicity, age, gender, and genetic factors. Warfarin acts through interference with the recycling of vitamin K in the liver. It has been reported that mutations in VKORC1, CYP2C9, and GGCX cause warfarin resistance.

UniProtKB/Swiss-Prot : 73 Coumarin resistance: A condition characterized by partial or complete resistance to warfarin or other 4-hydroxycoumarin derivatives. These drugs are used as anti-coagulants for the prevention of thromboembolic diseases in subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement.

Related Diseases for Coumarin Resistance

Diseases related to Coumarin Resistance via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 1121)
# Related Disease Score Top Affiliating Genes
1 vitamin k deficiency bleeding 30.1 VKORC1 F9
2 thrombosis 29.6 VKORC1 F9 CYP4F2
3 atrial fibrillation 29.1 VKORC1 CYP4F2 CYP2C9
4 severe cutaneous adverse reaction 28.9 VKORC1 CYP2C9
5 multidrug-resistant tuberculosis 11.6
6 mycobacterium abscessus 11.4
7 mesial temporal lobe epilepsy with hippocampal sclerosis 11.4
8 hemimegalencephaly 11.3
9 ceroid lipofuscinosis, neuronal, 2 11.0
10 epilepsy with bilateral occipital calcifications 11.0
11 cerebral creatine deficiency syndrome 1 11.0
12 congenital disorder of glycosylation, type il 11.0
13 leukodystrophy, hypomyelinating, 14 11.0
14 neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity 11.0
15 reye syndrome 11.0
16 ring chromosome 20 11.0
17 pulmonary tuberculosis 10.9
18 epilepsy 10.9
19 mycobacterium tuberculosis 1 10.8
20 human immunodeficiency virus type 1 10.8
21 ovarian cancer 10.8
22 malaria 10.8
23 focal epilepsy 10.7
24 myeloma, multiple 10.7
25 lung cancer 10.7
26 myeloid leukemia 10.7
27 colorectal cancer 10.6
28 breast cancer 10.6
29 leukemia, acute myeloid 10.6
30 leukemia 10.6
31 bacterial infectious disease 10.6
32 leukemia, acute lymphoblastic 10.6
33 temporal lobe epilepsy 10.6
34 visual epilepsy 10.6
35 seizure disorder 10.6
36 immune deficiency disease 10.5
37 hepatocellular carcinoma 10.5
38 small cell cancer of the lung 10.5
39 typhoid fever 10.5
40 gastric cancer 10.5
41 hepatitis b 10.5
42 plasmodium falciparum malaria 10.5
43 osteogenic sarcoma 10.5
44 diarrhea 10.5
45 leprosy 3 10.5
46 leukemia, chronic myeloid 10.5
47 hansen's disease 10.5
48 glioblastoma multiforme 10.5
49 acute cystitis 10.5
50 human immunodeficiency virus infectious disease 10.5

Graphical network of the top 20 diseases related to Coumarin Resistance:



Diseases related to Coumarin Resistance

Symptoms & Phenotypes for Coumarin Resistance

Human phenotypes related to Coumarin Resistance:

31
# Description HPO Frequency HPO Source Accession
1 abnormality of metabolism/homeostasis 31 HP:0001939
2 abnormality of blood and blood-forming tissues 31 HP:0001871

Symptoms via clinical synopsis from OMIM:

56
Heme:
warfarin resistance

Lab:
decreased affinity of liver receptors for coumarin

Clinical features from OMIM:

122700

Drugs & Therapeutics for Coumarin Resistance

Drugs for Coumarin Resistance (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 662)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Iron Approved, Experimental Phase 4 15438-31-0, 7439-89-6 27284 23925
2
Rilpivirine Approved Phase 4 500287-72-9
3
Ceftriaxone Approved Phase 4 73384-59-5 5361919 5479530
4
Guaifenesin Approved, Investigational, Vet_approved Phase 4 93-14-1 3516
5
Artesunate Approved, Investigational Phase 4 88495-63-0 6917864 5464098
6
Esomeprazole Approved, Investigational Phase 4 161796-78-7, 119141-88-7, 161973-10-0 9568614 4594
7
Pantoprazole Approved Phase 4 102625-70-7 4679
8
Colistin Approved Phase 4 1264-72-8, 1066-17-7 5311054
9
tannic acid Approved Phase 4 1401-55-4
10
Benzocaine Approved, Investigational Phase 4 94-09-7, 1994-09-7 2337
11
Stavudine Approved, Investigational Phase 4 3056-17-5 18283
12
Indinavir Approved Phase 4 150378-17-9 5362440
13
Potassium citrate Approved, Investigational, Vet_approved Phase 4 866-84-2
14
Peginterferon alfa-2a Approved, Investigational Phase 4 198153-51-4 5360545
15
Enfuvirtide Approved, Investigational Phase 4 159519-65-0 16130199
16
Piperazine Approved, Vet_approved Phase 4 110-85-0 4837
17
Methadone Approved Phase 4 76-99-3 4095
18
Abacavir Approved, Investigational Phase 4 136470-78-5 441300 65140
19
Tacrolimus Approved, Investigational Phase 4 104987-11-3 445643 439492 6473866
20
Histamine Approved, Investigational Phase 4 51-45-6 774
21
Amprenavir Approved, Investigational Phase 4 161814-49-9 65016
22
Sulfamethoxazole Approved Phase 4 723-46-6 5329
23
Trimethoprim Approved, Vet_approved Phase 4 738-70-5 5578
24
Omeprazole Approved, Investigational, Vet_approved Phase 4 73590-58-6 4594
25
Atorvastatin Approved Phase 4 134523-00-5 60823
26
Lansoprazole Approved, Investigational Phase 4 103577-45-3 3883
27
Dexlansoprazole Approved, Investigational Phase 4 103577-45-3, 138530-94-6 9578005
28
Naltrexone Approved, Investigational, Vet_approved Phase 4 16590-41-3 5360515
29
Fosamprenavir Approved Phase 4 226700-79-4 131536
30
Triamcinolone Approved, Vet_approved Phase 4 124-94-7 31307
31
Propofol Approved, Investigational, Vet_approved Phase 4 2078-54-8 4943
32
Fluconazole Approved, Investigational Phase 4 86386-73-4 3365
33
Nitazoxanide Approved, Investigational, Vet_approved Phase 4 55981-09-4 41684
34
Topotecan Approved, Investigational Phase 4 123948-87-8, 119413-54-6 60700
35
Fosfomycin Approved Phase 4 23155-02-4 446987
36
Azithromycin Approved Phase 4 83905-01-5 447043 55185
37
Vancomycin Approved Phase 4 1404-90-6 14969 441141
38
Rabeprazole Approved, Investigational Phase 4 117976-89-3 5029
39
Meropenem Approved, Investigational Phase 4 96036-03-2, 119478-56-7 441130 64778
40
Gemcitabine Approved Phase 4 95058-81-4 60750
41
Cisplatin Approved Phase 4 15663-27-1 2767 441203 84093
42
Chlorhexidine Approved, Vet_approved Phase 4 55-56-1 9552079 2713
43
Iodine Approved, Investigational Phase 4 7553-56-2 807
44
Povidone Approved Phase 4 9003-39-8
45
Povidone-iodine Approved Phase 4 25655-41-8
46
Clarithromycin Approved Phase 4 81103-11-9 84029
47
Tetracycline Approved, Vet_approved Phase 4 60-54-8 5353990
48
Proguanil Approved Phase 4 500-92-5 4923
49
Atovaquone Approved Phase 4 95233-18-4 74989
50
Albendazole Approved, Vet_approved Phase 4 54965-21-8 2082

Interventional clinical trials:

(show top 50) (show all 965)
# Name Status NCT ID Phase Drugs
1 Evaluation of Antiplatelet Drug Resistance in Taiwanese With VASP & Platelet Mapping™ Assay Unknown status NCT01023360 Phase 4 Clopidogrel and proton pump inhibitors
2 Research on the Antiretroviral Therapy and Immune Reconstitution on Chinese HIV/AIDS Patients Unknown status NCT00872417 Phase 4 first line ARV (3TC+NVP+D4T or 3TC+NVP+AZT);second line ARV therapy (3TC+TDF+LPV/RTV)
3 Combination or Sequential Therapy of Peginterferon Alfa-2a and Entecavir for Hepatitis B e Antigen-positive Patients With Chronic Hepatitis B Unknown status NCT01906580 Phase 4 Peg-IFNα-2a;Entecavir
4 An Open Pilot Study to Evaluate the Efficacy and Safety, Tolerability of Raltegravir(RAL)in Treatment-experienced HIV-1 Infected Adult Chinese Patients Unknown status NCT01201239 Phase 4 raltegravir
5 Randomized Study Comparing Nucleoside Analogues Plus Tenofovir and Nucleoside Analogues Plus Adefovir in Chronic Hepatitis B Patients With Suboptimal Response to Adefovir-based Combination Therapy Due to Nucleoside Analogues Resistance Unknown status NCT01595633 Phase 4 Switching from adefovir (10mg/day) to tenofovir (300mg/day)
6 The Optimizing Treatment of Peginterferon Alpha in HBeAg-negative Chronic Hepatitis B Virus Patients With Low Level HBsAg Unknown status NCT02893124 Phase 4 peginterferon alfa
7 A Randomised Controlled Trial of a Strategy of Switching to Boosted PI Monotherapy Versus Continuing Combination ART for the Long-term Management of HIV-1 Infected Patients Who Have Achieved Sustained Virological Suppression on HAART Unknown status NCT01230580 Phase 4 Protease Inhibitor;Standard-of-care Antiretroviral therapy
8 Entecavir and Peginterferon Alfa-2a Sequential Therapy Versus Peginterferon Alfa-2a Monotherapy for HBeAg Negative Chronic Hepatitis B Unknown status NCT00917761 Phase 4 Entecavir and peginterferon (Pegasys) (52 weeks);Peginterferon (Pegasys) (96 weeks);Peginterferon (Pegasys) (48 weeks)
9 Entecavir and Peginterferon Alfa-2a Sequential Therapy Versus Peginterferon Alfa-2a Monotherapy for HBeAg Positive Chronic Hepatitis B Unknown status NCT00921180 Phase 4 Entecavir and peginterferon alfa-2a;Placebo and peginterferon
10 10-Day Antimicrobial Susceptibility Testing Guided Triple Therapy Versus 14-Day Empirical Tailored Therapy for the First-line Treatment of Helicobacter Pylori Infection-A Randomized Controlled Trail Unknown status NCT03571230 Phase 4 two sensitive antibiotics(amoxicillin, clarithromycin, metronidazole, tinidazole, levofloxacin, furazolidone and tetracycline);two antibiotics based on personal medication history(amoxicillin,clarithromycin,furazolidone);one proton pump inhibitor(PPI);Colloidal Bismuth Pectin;two antibiotics for failed eradication(tetracyclin,furazolidone)
11 Evaluation of the Public Health Impact and Cost Effectiveness of Seasonal Intermittent Preventive Treatment in Children in Senegal Unknown status NCT00712374 Phase 4 sulfadoxine-pyrimethamine plus amodiaquine
12 International Multicenter Trial for the Evaluation of a Four-Drug Fixed Dose Combined Tablet Daily in the Initial Intensive Phase of Chemotherapy Followed by a Two-Drug Fixed Dose Combined Tablet Three Times a Week in the Continuation Phase for the Treatment of Pulmonary Tuberculosis Unknown status NCT00216333 Phase 4 combined fixed dose combination
13 New Super-short Course Regimen for Retreatment Pulmonary Tuberculosis Unknown status NCT02331823 Phase 4 Isoniazid Aminosalicylate Tablets;Streptomycin injectable
14 A Phase IV, Multicentre Randomized Prospective Open Label Study to Evaluate Whether Switching From Current cART to Triumeq in Addition to Adherence Support Will Enhance Virologic Control and Adherence in Vulnerable Populations Relative to Adherence Support Alone Unknown status NCT02354053 Phase 4 Switch to Triumeq
15 Pharmacokinetics/ Pharmacodynamics (PK/PD) Study of Vancomycin in the Treatment of Methicillin-resistant Staphylococcus Aureus(MRSA) Blood Stream Infection (Septicemia) and Endocarditis in Chinese Patients Unknown status NCT02443064 Phase 4 Vancomycin
16 Combination With Intravenous Iron Supplementation or Doubling Erythropoietin Dose for Patients With Chemotherapy-induced Anaemia Inadequately Responsive to Initial Erythropoietin Treatment Alone Unknown status NCT02731378 Phase 4 Erythropoietins (EPO);Aggressive iron dextran supplementation;Erythropoietins (EPO);Sustained iron dextran supplementation
17 Evaluating the Efficacy of Chloroquine for the Treatment of Plasmodium Vivax Infections in Central Vietnam Unknown status NCT02610686 Phase 4 Chloroquine
18 Pegasys Plus Entecavir Versus Entecavir Versus Pegasys for Hepatitis B e Antigen-Negative Chronic Hepatitis B Unknown status NCT01925820 Phase 4 Pegasys&Entecavir
19 An Open-label Rollover Study in Chinese Patients After Finishing a 3-year Randomize Trial for Chronic Hepatitis B With High Serum Viral Load But Mild Elevated Aminotransferase Unknown status NCT02463019 Phase 4 Tenofovir Disoproxil Fumarate
20 Entecavir Combined Short-term Intravenous Hepatitis B Immune Globulin (HBIG) to Prevent Hepatitis B Recurrence After Liver Transplantation Unknown status NCT02417207 Phase 4 Entecavir combined long-term low-dose HBIG group intramuscular;Entecavir combined HBIG group short-term high-dose intravenous
21 Assessment of in Vivo and in Vitro Efficacy of Combined Artesunate/Mefloquine Therapy for Treatment of Uncomplicated Plasmodium Falciparum Infection in the Peruvian Amazon Unknown status NCT02084602 Phase 4 Artesunate;Mefloquine
22 Comparing the Effectiveness of 5 Artemisinin Combination Treatment Regimens in the Treatment of Uncomplicated Falciparum Malaria Unknown status NCT00902811 Phase 4 AM(FDC);AM(LT);AL;DP;AA(FDC)
23 A Phase IV 48 Week, Open Label, Pilot Study of Darunavir Boosted by Cobicistat in Combination With Rilpivirine to Treat HIV+ Naïve Subjects (PREZENT) Unknown status NCT02404233 Phase 4 darunavir/cobicistat;rilpivirine
24 Pegasys Plus Entecavir Versus Entecavir Alone for Hepatitis Be Antigen-Positive Chronic Hepatitis B Unknown status NCT00597259 Phase 4 Pegasys plus Entecavir;Entecavir
25 Pharmacokinetic Interaction Between Coartem® and Either Nevirapine, Efavirenz or Rifampicin in HIV Positive Ugandan Patients Unknown status NCT00620438 Phase 4 Lumefantrine-artemether and nevirapine;lumefantrine-artemether and efavirenz;Lumefantrine-artemether and rifampicin
26 Efficacy of Artesunate Monotherapy and Dihydroartemisinin - Piperaquine in Patients With Uncomplicated Falciparum Malaria in Central Vietnam Unknown status NCT02604966 Phase 4 Artesunate (AS) group;DHA - PPQ group
27 A Randomised Comparator Study to Assess the Relative Efficacy of Genotypic Versus Virtual Phenotypic Resistance Tests in Treatment Experienced Patients With HIV Infection for Whom a Change in Therapy is Indicated Completed NCT00262717 Phase 4
28 Intermittent Preventive Treatment of Malaria With Sulfadoxine-Pyrimethamine in Different Zones of Drug Resistance in Rwanda Completed NCT00372632 Phase 4 Sulfadoxine-Pyrimethamine;placebo
29 Multicenter Open-label RCT to Compare Colistin Alone vs. Colistin Plus Meropenem Completed NCT01732250 Phase 4 Colistin;Meropenem
30 Treatment of Uncomplicated Childhood Malaria by an Artemisinin Derivative in Combination With Lumefantrine. Efficacy, Safety and Genotyping. Completed NCT00336375 Phase 4 artemether-lumefantrine
31 Randomized, Open-Labelled Study Evaluating the Antiviral Efficacy, Safety, and Tolerability of Continuing Lamivudine Therapy or Switching to Entecavir in Subjects With Chronic Hepatitis B With Detectable HBV DNA Completed NCT00625560 Phase 4 Entecavir;Lamivudine
32 Three Generic Nevirapine-Based Antiretroviral Treatments in Chinese Patients:Multicentric Observation Cohort Completed NCT00618176 Phase 4 Zidovudine (AZT)+ Didanosine (ddI)+ Nevirapine (NVP);Stavudine (d4T), Lamivudine (3TC), Nevirapine (NVP);Zidovudine (AZT), Lamivudine (3TC), Nevirapine (NVP)
33 A Phase IV Study to Evaluate the Efficacy, Safety and Tolerability of Tenofovir DF in Asian-American Adults With Chronic Hepatitis B Infection Completed NCT00736190 Phase 4 Tenofovir disoproxil fumarate
34 Antibiotic Susceptibility-based Tailored Therapy for Helicobacter Pylori Treatment in Patients With Penicillin Allergy: a Prospective Clinical Trial Completed NCT03708848 Phase 4 Esomeprazole;Bismuth Potassium Citrate;Clarithromycin;Metronidazole;Levofloxacin;Tetracycline
35 A Single-Arm Study Evaluating the Efficay and Safety of Tenofovir DF,Lamivudine and Efavirenz in Adults With HIV/HBV Coinfection Completed NCT01751555 Phase 4 Regimen:TDF+3TC+EFV
36 Efficacy of Amodiaquine-artesunate in the Treatment of Symptomatic, Uncomplicated Plasmodium Falciparum Malaria Among 6-59 Month Old Children at an IPTi Site in Rural Western Kenya Completed NCT00425763 Phase 4 AQAS
37 Study of Policosanol to Improve High on Clopidogrel Platelet Reactivity After Percutaneous Coronary Stent Implantation(Spirit) Completed NCT01371058 Phase 4 high maintenance clopidogrel;routine dual antiplatelet;policosanol plus dual antiplatelet
38 Partial Treatment Interruptions in HIV-1 Patients With Multi-Drug Resistant Virus Completed NCT00187551 Phase 4
39 Different Drug Combinations Against Hookworm Infection in School-aged Children in the Lao People's Democratic Republic, a Single Blind, Randomised Controlled Trial Completed NCT03278431 Phase 4 Albendazole;Pyrantel Pamoate;Oxantel Pamoate;Mebendazole
40 A Randomised Open-label Study Comparing the Safety and Efficacy of Ritonavir Boosted Lopinavir and 2-3N(t)RTI Backbone Versus Ritonavir Boosted Lopinavir and Raltegravir in Participants Virologically Failing First-line NNRTI/2N(t)RTI Therapy Completed NCT00931463 Phase 4 raltegravir;2N(t)RTI;Ritonavir-boosted lopinavir
41 Efficacy and Safety of Artesunate-amodiaquine and Dihydroartemisinin-piperaquine for the Treatment of Uncomplicated Falciparum Malaria in Mainland Tanzania Completed NCT03431714 Phase 4 Artesunate amodiaquine
42 Randomized, Open-Labeled Study Evaluating the Antiviral Efficacy, Safety, and Tolerability of Continuing Lamivudine Therapy or Switching to Entecavir in Subjects With Chronic Hepatitis B Who Achieved Undetectable HBV DNA Completed NCT00625339 Phase 4 Entecavir;Lamivudine
43 Randomized, Open-Labeled Study Evaluating the Antiviral Efficacy, Safety, and Tolerability of Continuing Lamivudine Therapy or Switching to Entecavir in Subjects With Chronic Hepatitis B Who Achieved Undetectable HBV DNA Completed NCT00637663 Phase 4 Entecavir;Lamivudine
44 Nevirapine vs Ritonavir-boosted Lopinavir in ART HIV-infected Adults in a Resource-limited Setting; a Randomized, Multicenter, Parallel Group Study Completed NCT01772940 Phase 4 nevirapine;ritonavir-boosted Lopinavir;Tenofovir/emtricitabine;Zidovudine/lamivudine
45 Rapid Detection of Rifampin and Isoniazid Resistance by PCR Before Tuberculosis (TB) Treatment Initiation: a National Multicenter Randomized Clinical Trial Completed NCT02231229 Phase 4 conventional therapy
46 Open-label Multicenter Study to Assess the Efficacy, the Tolerability and the Adherence of a Once Daily (QD) Taken Antiretroviral Therapy (ART) Containing the NtRTI Tenofovir DF 300 mg in Combination With the Best Suitable Once a Day Regimen Being 1 NRTI Plus 1 PI or 1 NRTI Plus 1 NNRTI in HIV-1-infected IVDU- Patients With Opiate Substitution Being Either Antiretroviral-naive or With Suppressed Viral Load and Without a History of Virological Failure Completed NCT00324688 Phase 4 Viread
47 An Evaluation of the Impact of Cotrimoxazole Prophylaxis for HIV-Infected Adults on the Development of Antifolate Resistance Among Plasmodium Falciparum, Streptococcus Pneumoniae, and Escherichia Coli Completed NCT00137657 Phase 4 Cotrimoxazole (trimethoprim sulfamethoxazole)
48 Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects Completed NCT00930670 Phase 4 Rosuvastatin-omeprazole;Rosuvastatin-pantoprazole;Rosuvastatin-esomeprazole;Rosuvastatin-ranitidine;Atorvastatin-omeprazole;Atorvastatin-pantoprazole;Atorvastatin-esomeprazole;Atorvastatin-ranitidine
49 Pharmacokinetics of Miltefosine in Children and Adults: Implications for the Treatment of Cutaneous Leishmaniasis in Colombia. Completed NCT01462500 Phase 4 Miltefosine
50 Helicobacter Pylori Eradication Rates of Bismuth-containing Quadruple Therapy vs Modified Quadruple Therapy in Korea; Open-label, Randomized Controlled Trial Completed NCT03665428 Phase 4 PAMB treatment (modified quadruple therapy);PBMT treatment (bismuth-containing quadruple therapy)

Search NIH Clinical Center for Coumarin Resistance

Cochrane evidence based reviews: drug resistance

Genetic Tests for Coumarin Resistance

Genetic tests related to Coumarin Resistance:

# Genetic test Affiliating Genes
1 Warfarin Response 29 CYP2A6 CYP2C9 F9 VKORC1

Anatomical Context for Coumarin Resistance

MalaCards organs/tissues related to Coumarin Resistance:

40
Lung, Breast, Testes, Myeloid, Heart, Liver, B Cells

Publications for Coumarin Resistance

Articles related to Coumarin Resistance:

(show top 50) (show all 223)
# Title Authors PMID Year
1
Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. 56 6 61 54
14765194 2004
2
Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements. 6 56
20555338 2010
3
VKORC1 polymorphisms, haplotypes and haplotype groups on warfarin dose among African-Americans and European-Americans. 56 6
18855533 2008
4
A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. 6 56
15888487 2005
5
The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes. 6 56
2322567 1990
6
Warfarin pharmacogenetics: CYP2C9 and VKORC1 genotypes predict different sensitivity and resistance frequencies in the Ashkenazi and Sephardi Jewish populations. 61 6
18252229 2008
7
A coding VKORC1 Asp36Tyr polymorphism predisposes to warfarin resistance. 61 6
17110455 2007
8
A gene-anchored map position of the rat warfarin-resistance locus, Rw, and its orthologs in mice and humans. 61 56
10961907 2000
9
Hereditary warfarin resistance. Investigation of a rare phenomenon. 61 56
3977518 1985
10
Warfarin resistance in the rat. 56 61
5671000 1968
11
Warfarin resistance. 61 56
6023007 1967
12
Clinical Practice Recommendations on Genetic Testing of CYP2C9 and VKORC1 Variants in Warfarin Therapy. 6
26186657 2015
13
Do pharmacogenetics have a role in the dosing of vitamin K antagonists? 6
24251364 2013
14
A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose. 56
19300499 2009
15
Estimation of the warfarin dose with clinical and pharmacogenetic data. 56
19228618 2009
16
CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin dosing variability in the Italian population. 56
19207028 2009
17
A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose. 56
18535201 2008
18
CYP4F2 genetic variant alters required warfarin dose. 56
18250228 2008
19
A rapid-ACCE review of CYP2C9 and VKORC1 alleles testing to inform warfarin dosing in adults at elevated risk for thrombotic events to avoid serious bleeding. 6
18281915 2008
20
Pharmacogenetic testing of CYP2C9 and VKORC1 alleles for warfarin. 6
18281922 2008
21
Polymorphisms in the VKORC1 gene are strongly associated with warfarin dosage requirements in patients receiving anticoagulation. 6
16611750 2006
22
Different contributions of polymorphisms in VKORC1 and CYP2C9 to intra- and inter-population differences in maintenance dose of warfarin in Japanese, Caucasians and African-Americans. 56
16424822 2006
23
Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. 6
15805193 2005
24
CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis. 6
15714076 2005
25
Upstream and coding region CYP2C9 polymorphisms: correlation with warfarin dose and metabolism. 6
15608560 2004
26
Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX, and X; proteins S and C; and gamma-glutamyl carboxylase) gene variants with warfarin sensitivity. 56
14656880 2004
27
Characterization of a novel CYP2A7/CYP2A6 hybrid allele (CYP2A6*12) that causes reduced CYP2A6 activity. 6
12325023 2002
28
Genetic polymorphism in exon 4 of cytochrome P450 CYP2C9 may be associated with warfarin sensitivity in Chinese patients. 6
11588061 2001
29
The use of long PCR to confirm three common alleles at the CYP2A6 locus and the relationship between genotype and smoking habit. 6
11281276 2000
30
Characterisation and PCR-based detection of a CYP2A6 gene deletion found at a high frequency in a Chinese population. 6
10217419 1999
31
Genetic variation of CYP2A6, smoking, and risk of cancer. 6
10093988 1999
32
Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. 6
10208645 1999
33
Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. 6
10073515 1999
34
Genotyping of human cytochrome P450 2A6 (CYP2A6), a nicotine C-oxidase. 6
9827545 1998
35
Nicotine metabolism defect reduces smoking. 6
9655391 1998
36
Genetic association between sensitivity to warfarin and expression of CYP2C9*3. 6
9352571 1997
37
A single amino acid substitution (Leu160His) in cytochrome P450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin. 6
9409631 1997
38
Missense mutations at ALA-10 in the factor IX propeptide: an insignificant variant in normal life but a decisive cause of bleeding during oral anticoagulant therapy. 6
9233593 1997
39
A mutation in the propeptide of Factor IX leads to warfarin sensitivity by a novel mechanism. 6
8833911 1996
40
The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. 6
8873220 1996
41
A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles. 6
7668294 1995
42
Molecular characterization of the murine Coh locus: an amino acid difference at position 117 confers high and low coumarin 7-hydroxylase activity in P450coh. 56
1302041 1992
43
The P450 superfamily: update on new sequences, gene mapping, and recommended nomenclature. 56
1991046 1991
44
Genetic variation between mice in their metabolism of coumarin and its derivatives. 56
566237 1978
45
Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. 56
646989 1978
46
Genetic variation in coumarin hydroxylase activity in the mouse (Mus musculus). 56
4366489 1974
47
The second reported kindred with hereditary resistance to oral anticoagulant drugs. 56
4192578 1970
48
Genetic control of dicumarol levels in man. 56
4177776 1968
49
HEREDITARY TRANSMISSION OF EXCEPTIONAL RESISTANCE TO COUMARIN ANTICOAGULANT DRUGS. THE FIRST REPORTED KINDRED. 56
14187664 1964
50
Pharmacodynamic resistance to warfarin is associated with nucleotide substitutions in VKORC1. 61 54
18680536 2008

Variations for Coumarin Resistance

ClinVar genetic disease variations for Coumarin Resistance:

6 (show all 29) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 VKORC1 NM_024006.4(VKORC1):c.-1639G>ASNV Likely benign, other 2211 rs9923231 16:31107689-31107689 16:31096368-31096368
2 APOE NM_000041.4(APOE):c.388T>C (p.Cys130Arg)SNV Likely pathogenic,risk factor 17864 rs429358 19:45411941-45411941 19:44908684-44908684
3 CYP2C9 NM_000771.4(CYP2C9):c.622T>G (p.Leu208Val)SNV Pathogenic 8410 rs72558191 10:96707676-96707676 10:94947919-94947919
4 F9 F9, ALA-10THRSNV Pathogenic 10659
5 F9 F9, ALA-10VALundetermined variant Pathogenic 10661
6 VKORC1 NM_024006.6(VKORC1):c.85G>T (p.Val29Leu)SNV Pathogenic 2207 rs104894539 16:31105966-31105966 16:31094645-31094645
7 VKORC1 NM_024006.6(VKORC1):c.134T>C (p.Val45Ala)SNV Pathogenic 2208 rs104894540 16:31105917-31105917 16:31094596-31094596
8 VKORC1 NM_024006.6(VKORC1):c.172A>G (p.Arg58Gly)SNV Pathogenic 2209 rs104894541 16:31105879-31105879 16:31094558-31094558
9 VKORC1 NM_024006.6(VKORC1):c.383T>G (p.Leu128Arg)SNV drug response 2210 rs104894542 16:31102564-31102564 16:31091243-31091243
10 APOE NC_000019.9:g.45408836T>GSNV drug response 619951 19:45408836-45408836 19:44905579-44905579
11 APOE NM_000041.4(APOE):c.43+520G>ASNV drug response 619952 19:45410444-45410444 19:44907187-44907187
12 APOE NC_000019.9:g.45414451T>CSNV drug response 619953 19:45414451-45414451 19:44911194-44911194
13 CYP2A6 NM_000762.5(CYP2A6):c.479T>A (p.Leu160His)SNV drug response 16969 rs1801272 19:41354533-41354533 19:40848628-40848628
14 CYP2A6 CYP2A6*12Adeletion drug response 16973 19:41354669-41387493 19:40848764-40881588
15 APOE NM_000041.2(APOE):c.526C>T (p.Arg176Cys)SNV drug response 17848 rs7412 19:45412079-45412079 19:44908822-44908822
16 VKORC1 NM_024006.6(VKORC1):c.106G>T (p.Asp36Tyr)SNV drug response 2212 rs61742245 16:31105945-31105945 16:31094624-31094624
17 CYP2C9 NM_000771.3(CYP2C9):c.1075A>C (p.Ile359Leu)SNV drug response 8408 rs1057910 10:96741053-96741053 10:94981296-94981296
18 CYP2C9 NM_000771.3(CYP2C9):c.430C>T (p.Arg144Cys)SNV drug response 8409 rs1799853 10:96702047-96702047 10:94942290-94942290
19 VKORC1 NM_024006.6(VKORC1):c.174-136C>TSNV drug response 37344 rs9934438 16:31104878-31104878 16:31093557-31093557
20 VKORC1 NM_024006.5(VKORC1):c.-226-1362dupGduplication drug response 60671 rs397509427 16:31107637-31107638 16:31096316-31096317
21 VKORC1 NM_024006.5(VKORC1):c.-226-1413G=SNV drug response 166563 rs9923231 16:31107689-31107689 16:31096368-31096368
22 APOB NM_000384.3(APOB):c.1594C>T (p.Arg532Trp)SNV Conflicting interpretations of pathogenicity 255979 rs13306194 2:21252534-21252534 2:21029662-21029662
23 VKORC1 NM_024006.6(VKORC1):c.196G>A (p.Val66Met)SNV Conflicting interpretations of pathogenicity 692018 16:31104720-31104720 16:31093399-31093399
24 APOB NM_000384.3(APOB):c.1853C>T (p.Ala618Val)SNV Benign/Likely benign 128420 rs679899 2:21250914-21250914 2:21028042-21028042
25 APOB NM_000384.3(APOB):c.293C>T (p.Thr98Ile)SNV Benign/Likely benign 128422 rs1367117 2:21263900-21263900 2:21041028-21041028
26 APOB NM_000384.3(APOB):c.7545C>T (p.Thr2515=)SNV Benign 128425 rs693 2:21232195-21232195 2:21009323-21009323
27 APOB NM_000384.3(APOB):c.13013G>A (p.Ser4338Asn)SNV Benign 128418 rs1042034 2:21225281-21225281 2:21002409-21002409
28 CYP2C9 NM_000771.4(CYP2C9):c.1075= (p.Ile359=)SNV no interpretation for the single variant 242623 rs1057910 10:96741053-96741053 10:94981296-94981296
29 CYP2C9 NM_000771.4(CYP2C9):c.430= (p.Arg144=)SNV no interpretation for the single variant 242622 rs1799853 10:96702047-96702047 10:94942290-94942290

UniProtKB/Swiss-Prot genetic disease variations for Coumarin Resistance:

73 (show all 18)
# Symbol AA change Variation ID SNP ID
1 VKORC1 p.Val29Leu VAR_021821 rs104894539
2 VKORC1 p.Val45Ala VAR_021822 rs104894540
3 VKORC1 p.Arg58Gly VAR_021823 rs104894541
4 VKORC1 p.Leu128Arg VAR_021825 rs104894542
5 VKORC1 p.Ala26Thr VAR_065785 rs770703948
6 VKORC1 p.Asp36Gly VAR_065786
7 VKORC1 p.Asp36Tyr VAR_065787 rs61742245
8 VKORC1 p.Ser52Trp VAR_065788
9 VKORC1 p.Ser56Phe VAR_065789
10 VKORC1 p.Trp59Cys VAR_065790
11 VKORC1 p.Trp59Leu VAR_065791
12 VKORC1 p.Val66Gly VAR_065792
13 VKORC1 p.Val66Met VAR_065793 rs72547529
14 VKORC1 p.Gly71Ala VAR_065794
15 VKORC1 p.Asn77Ser VAR_065795
16 VKORC1 p.Asn77Tyr VAR_065796 rs755767348
17 VKORC1 p.Ile123Asn VAR_065797
18 VKORC1 p.Tyr139His VAR_065798

Expression for Coumarin Resistance

Search GEO for disease gene expression data for Coumarin Resistance.

Pathways for Coumarin Resistance

Pathways related to Coumarin Resistance according to KEGG:

36
# Name Kegg Source Accession
1 Drug metabolism - cytochrome P450 hsa00982

Pathways related to Coumarin Resistance according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.55 CYP4F2 CYP2C9
2
Show member pathways
11.26 CYP2C9 CYP2A6
3
Show member pathways
11.15 CYP4F2 CYP2C9
4
Show member pathways
11 CYP2C9 CYP2A6
5 10.87 CYP2C9 CYP2A6
6
Show member pathways
10.75 CYP4F2 CYP2C9
7 10.64 CYP2C9 CYP2A6
8 10.46 CYP2C9 CYP2A6
9
Show member pathways
10.26 CYP2C9 CYP2A6
10 9.98 VKORC1 F9 CYP4F2

GO Terms for Coumarin Resistance

Cellular components related to Coumarin Resistance according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 intracellular membrane-bounded organelle GO:0043231 9.56 VKORC1 CYP4F2 CYP2C9 CYP2A6
2 endoplasmic reticulum membrane GO:0005789 9.35 VKORC1 MCFD2 CYP4F2 CYP2C9 CYP2A6
3 organelle membrane GO:0031090 9.33 CYP4F2 CYP2C9 CYP2A6
4 endoplasmic reticulum GO:0005783 9.1 VKORC1 MCFD2 CYP4F2 CYP2C9 CYP2A6 APOE

Biological processes related to Coumarin Resistance according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.73 VKORC1 CYP4F2 CYP2C9 CYP2A6
2 lipid metabolic process GO:0006629 9.69 CYP4F2 CYP2C9 APOE
3 blood coagulation GO:0007596 9.5 VKORC1 F9 CYP4F2
4 cholesterol metabolic process GO:0008203 9.49 CYP2C9 APOE
5 xenobiotic metabolic process GO:0006805 9.48 CYP2C9 CYP2A6
6 arachidonic acid metabolic process GO:0019369 9.46 CYP4F2 CYP2C9
7 steroid metabolic process GO:0008202 9.43 CYP2C9 CYP2A6 APOE
8 exogenous drug catabolic process GO:0042738 9.4 CYP2C9 CYP2A6
9 organic acid metabolic process GO:0006082 9.37 CYP2C9 CYP2A6
10 omega-hydroxylase P450 pathway GO:0097267 9.16 CYP4F2 CYP2C9
11 epoxygenase P450 pathway GO:0019373 9.13 CYP4F2 CYP2C9 CYP2A6
12 drug metabolic process GO:0017144 8.92 VKORC1 CYP4F2 CYP2C9 CYP2A6

Molecular functions related to Coumarin Resistance according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.67 VKORC1 CYP4F2 CYP2C9 CYP2A6
2 heme binding GO:0020037 9.5 CYP4F2 CYP2C9 CYP2A6
3 steroid hydroxylase activity GO:0008395 9.46 CYP2C9 CYP2A6
4 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen GO:0016712 9.43 CYP2C9 CYP2A6
5 iron ion binding GO:0005506 9.43 CYP4F2 CYP2C9 CYP2A6
6 aromatase activity GO:0070330 9.4 CYP4F2 CYP2C9
7 monooxygenase activity GO:0004497 9.33 CYP4F2 CYP2C9 CYP2A6
8 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen GO:0016705 9.13 CYP4F2 CYP2C9 CYP2A6
9 arachidonic acid epoxygenase activity GO:0008392 8.8 CYP4F2 CYP2C9 CYP2A6

Sources for Coumarin Resistance

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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