CMRES
MCID: CMR002
MIFTS: 59

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 57 43 72 36 13 70
Warfarin Resistance 57 12 20 43 72 54 15
Warfarin Sensitivity 57 12 20 43 15 70
Warfarin Response 43 29 6
Poor Metabolism of Coumarin 43 72
Coumadin Sensitivity 20 43
Coumarin, Poor Metabolism of 57
Drug Resistance 44
Cmres 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant


HPO:

31
coumarin resistance:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0080665 DOID:0080666
OMIM® 57 122700
KEGG 36 H01205
MeSH 44 D004351
SNOMED-CT via HPO 68 191124002 263681008 34093004
UMLS 70 C0750384 C2608079

Summaries for Coumarin Resistance

MedlinePlus Genetics : 43 Warfarin sensitivity is a condition in which individuals have a low 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).Many people with warfarin sensitivity take longer than normal to break down (metabolize) warfarin. The medication remains active in their body longer than usual, so they require lower doses. These individuals are classified as "slow metabolizers" of warfarin. Other people with warfarin sensitivity do not need as much drug to prevent clots because their clot-forming process is naturally slower than average and can be stopped by low warfarin doses. If people with warfarin sensitivity take the average dose (or more) of warfarin, they are at risk of an overdose, which can cause abnormal bleeding in the brain, gastrointestinal tract, or other tissues, and may lead to serious health problems or death.Warfarin sensitivity 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 acquired immunodeficiency syndrome and aspirin resistance. 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 Metabolism. The drugs Rabeprazole and Tigecycline have been mentioned in the context of this disorder. Affiliated tissues include heart, lung and thyroid, 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.

GARD : 20 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® : 57 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. The dose requirement is highly variable, both interindividually and interethnically (Yuan et al., 2005). 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) (Updated 20-May-2021)

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 : 72 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 793)
# Related Disease Score Top Affiliating Genes
1 acquired immunodeficiency syndrome 31.0 F9 APOE APOB
2 aspirin resistance 30.8 F2 APOB
3 clopidogrel resistance 30.5 PPIG CYP3A5 CYP2C9 CYP2C19
4 hereditary combined deficiency of vitamin k-dependent clotting factors 30.3 VKORC1 GGCX
5 vascular disease 30.1 F2 CYP2C9 CYP2C19 APOE APOB
6 thrombosis 30.0 VKORC1 F9 F2 CYP4F2
7 active peptic ulcer disease 30.0 F2 CYP2C19
8 vitamin k deficiency bleeding 29.9 VKORC1L1 VKORC1 GGCX F9 F2
9 atrial fibrillation 29.8 VKORC1 F9 F2 CYP4F2
10 cerebrovascular disease 29.8 VKORC1 F2 CYP2C19 APOE APOB
11 bilirubin metabolic disorder 29.5 PPIG F9 F2 CYP3A5 CYP2D6 CYP2C9
12 heart disease 29.4 VKORC1 PPIG F2 CYP2D6 CYP2C9 CYP2C19
13 warfarin sensitivity, x-linked 11.7
14 mycobacterium abscessus 11.1
15 mycobacterium tuberculosis 1 11.0
16 human immunodeficiency virus type 1 10.9
17 pulmonary tuberculosis 10.9
18 immune deficiency disease 10.9
19 ovarian cancer 10.8
20 myeloma, multiple 10.8
21 multidrug-resistant tuberculosis 10.8
22 malaria 10.8
23 leukemia, acute myeloid 10.8
24 myeloid leukemia 10.7
25 leukemia 10.7
26 leukemia, acute lymphoblastic 10.7
27 small cell cancer of the lung 10.7
28 lung cancer 10.7
29 hepatitis b 10.7
30 gastric cancer 10.7
31 colorectal cancer 10.6
32 osteogenic sarcoma 10.6
33 breast cancer 10.6
34 epilepsy 10.6
35 human immunodeficiency virus infectious disease 10.6
36 disease by infectious agent 10.6
37 glioblastoma 10.6
38 hepatocellular carcinoma 10.6
39 leukemia, chronic myeloid 10.6
40 lung cancer susceptibility 3 10.6
41 leprosy 3 10.6
42 hansen's disease 10.6
43 plasmodium falciparum malaria 10.6
44 pancreatic cancer 10.5
45 lymphoma 10.5
46 b-cell lymphoma 10.5
47 glioma 10.5
48 ovarian epithelial cancer 10.5
49 glial tumor 10.5
50 kala-azar 1 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®:

57 (Updated 20-May-2021)
Hematology:
warfarin resistance
warfarin sensitivity

Laboratory Abnormalities:
warfarin resistance
warfarin sensitivity

Clinical features from OMIM®:

122700 (Updated 20-May-2021)

MGI Mouse Phenotypes related to Coumarin Resistance:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.44 APOB APOE CYP3A5 CYP4F2 EPHX1 F2

Drugs & Therapeutics for Coumarin Resistance

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

(show top 50) (show all 371)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Rabeprazole Approved, Investigational Phase 4 117976-89-3 5029
2
Tigecycline Approved Phase 4 220620-09-7 5282044
3
Acetazolamide Approved, Vet_approved Phase 4 59-66-5 1986
4
Methylprednisolone Approved, Vet_approved Phase 4 83-43-2 6741
5
Rufinamide Approved Phase 4 106308-44-5 129228
6
Phenytoin Approved, Vet_approved Phase 4 57-41-0 1775
7
Vigabatrin Approved Phase 4 60643-86-9, 68506-86-5 5665
8
Clonazepam Approved, Illicit Phase 4 1622-61-3 2802
9
Prednisolone Approved, Vet_approved Phase 4 50-24-8 5755
10
Prednisolone acetate Approved, Vet_approved Phase 4 52-21-1
11
Clobazam Approved, Illicit Phase 4 22316-47-8 2789
12
Oxcarbazepine Approved Phase 4 28721-07-5 34312
13
Zonisamide Approved, Investigational Phase 4 68291-97-4 5734
14
Levetiracetam Approved Phase 4 102767-28-2 441341
15
Gabapentin Approved, Investigational Phase 4 60142-96-3 3446
16
Methylprednisolone hemisuccinate Approved Phase 4 2921-57-5
17
Prednisolone phosphate Approved, Vet_approved Phase 4 302-25-0
18
Ethosuximide Approved Phase 4 77-67-8 3291
19
Tiagabine Approved, Investigational Phase 4 115103-54-3 60648
20
Felbamate Approved Phase 4 25451-15-4 3331
21
Pregabalin Approved, Investigational Phase 4 148553-50-8 5486971
22
Nitrazepam Approved Phase 4 146-22-5 4506
23
Entecavir Approved, Investigational Phase 4 142217-69-4 153941
24
Bisoprolol Approved Phase 4 66722-44-9 2405
25
Spironolactone Approved Phase 4 1952-01-7, 52-01-7 5833
26
Stavudine Approved, Investigational Phase 4 3056-17-5 18283
27
Ranitidine Approved, Withdrawn Phase 4 66357-59-3, 66357-35-5, 82530-72-1 3001055
28
Pantoprazole Approved Phase 4 102625-70-7 4679
29
Omeprazole Approved, Investigational, Vet_approved Phase 4 73590-58-6 4594
30
Atorvastatin Approved Phase 4 134523-00-5 60823
31
Histamine Approved, Investigational Phase 4 51-45-6, 75614-87-8 774
32
Esomeprazole Approved, Investigational Phase 4 161796-78-7, 161973-10-0, 119141-88-7 9568614 4594
33
chloroquine Approved, Investigational, Vet_approved Phase 4 54-05-7 2719
34
Pyrimethamine Approved, Investigational, Vet_approved Phase 4 58-14-0 4993
35
Levoleucovorin Approved, Investigational Phase 4 68538-85-2 149436
36
Sulfadoxine Approved, Investigational Phase 4 2447-57-6 17134
37
Amodiaquine Approved, Investigational Phase 4 86-42-0 2165
38
Trimethoprim Approved, Vet_approved Phase 4 738-70-5 5578
39
Sulfamethoxazole Approved Phase 4 723-46-6 5329
40
Naltrexone Approved, Investigational, Vet_approved Phase 4 16590-41-3 5360515
41
Pyrazinamide Approved, Investigational Phase 4 98-96-4 1046
42
Isoniazid Approved, Investigational Phase 4 54-85-3 3767
43
Ethambutol Approved Phase 4 74-55-5 3279 14052
44
Enfuvirtide Approved, Investigational Phase 4 159519-65-0 16130199
45
Artesunate Approved, Investigational Phase 4 88495-63-0 6917864 5464098
46
Mefloquine Approved, Investigational Phase 4 53230-10-7 4046
47
Imipenem Approved Phase 4 64221-86-9, 74431-23-5 104838
48
Cilastatin Approved, Investigational Phase 4 82009-34-5 5280454 6435415
49
Gatifloxacin Approved, Investigational Phase 4 112811-59-3 5379
50
Amoxicillin Approved, Vet_approved Phase 4 26787-78-0 33613

Interventional clinical trials:

(show top 50) (show all 353)
# Name Status NCT ID Phase Drugs
1 Evaluating the Efficacy of Chloroquine for the Treatment of Plasmodium Vivax Infections in Central Vietnam Unknown status NCT02610686 Phase 4 Chloroquine
2 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
3 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
4 Evaluation of Antiplatelet Drug Resistance in Taiwanese With VASP & Platelet Mapping™ Assay Unknown status NCT01023360 Phase 4 Clopidogrel and proton pump inhibitors
5 Comparing Ketogenic Diet With the Most Appropriate Antiepileptic Drug- a Randomized Study of Children With Mental Retardation and Drug Resistant Epilepsy Unknown status NCT00552526 Phase 4 Antiepileptic drug (AED)
6 A Multicenter, Open-label, Prospective Study to Evaluate Antiviral Efficacy and Safety of Entecavir Plus Tenofovir Combination in Subjects With Multi-drug Resistant Chronic Hepatitis B Virus Infection Unknown status NCT01594905 Phase 4 Entecavir + Tenofovir (MDR group)
7 Effectiveness and Safety of Tigecycline for Therapy of Infections Caused by Multi-Drug Resistant Acinetobacter Baumannii Unknown status NCT01342731 Phase 4 Tigecycline
8 Optimum Treatment for Drug-Resistant Hypertension Unknown status NCT02369081 Phase 4 Spironolactone;Bisoprolol;Doxazosin;Placebo
9 Efficacy of Polymyxin B Against Infections Caused by Extensively Drug-resistant (XDR) Gram-Negative Bacteria Unknown status NCT02328183 Phase 4 Polymyxin B
10 Use Of High Dose Colistin in Multi Drug Resistant Gram Negative Infections in Critically Ill Adult Patients. Randomized Controlled Clinical Trial Unknown status NCT02162966 Phase 4 High Dose Colistin;Standard Dose Colistin
11 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)
12 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
13 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)
14 Non-Response to Naltrexone (NTX): Next Steps in Managing Alcoholism Completed NCT00115037 Phase 4 Naltrexone;placebo
15 Assessing Chloroquine Resistance of Plasmodium Vivax in Malaria Endemic Area Completed NCT02118090 Phase 4 Chloroquine sulfate;DHA-PP
16 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
17 Intermittent Preventive Treatment of Malaria With Sulfadoxine-Pyrimethamine in Different Zones of Drug Resistance in Rwanda Completed NCT00372632 Phase 4 Sulfadoxine-Pyrimethamine;placebo
18 Multicenter Open Non-Comparative Clinical Study to Evaluate the Efficacy and Safety of Three Months TAVANIC Course (Levofloxacin) in Combine Treatment of Multi-Drug-Resistant Tuberculosis (MDR-TB) Completed NCT00495339 Phase 4 Levofloxacin
19 The Pharmacokinetic Effect of Clarithromycin on the AUC0-12h of Linezolid in Multidrug-resistant and Extensively Drug-resistant Tuberculosis (MDR/XDR-TB) Patients Completed NCT01521364 Phase 4 Addition of different doses of clarithromycin.
20 Partial Treatment Interruptions in HIV-1 Patients With Multi-Drug Resistant Virus Completed NCT00187551 Phase 4
21 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
22 The Individualized M(X) Drug-resistant TB Treatment Strategy Study A Strategy to Improve Treatment Outcomes in Patients With Drug-resistant TB Recruiting NCT03237182 Phase 4 Individualized TB treatment with multiple drugs;Standardized TB treatment with multiple drugs
23 Comparison of Efficacy of Low Glycemic Index Therapy and Modified Atkins Diet Among Children With Drug Resistant Epilepsy: A Randomized Non-inferiority Trial Recruiting NCT03764956 Phase 4
24 Multicenter Therapeutic Efficacy Assessment of Pyronaridine-Artesunate (Pyramax®) and New Drug Combinations With Atovaquone-Proguanil for the Treatment of Uncomplicated P. Falciparum Malaria in Cambodia Recruiting NCT03726593 Phase 4 Artesunate and Pyronaridine;Atovaquone Proguanil and Artesunate Pyronaridine;Atovaquone Proguanil and Artesunate Mefloquine
25 Leveraging the Gut Microbiota in Pediatric Refractory Epilepsy: Safety and Feasibility of Oligofructose-enriched Inulin Supplementation for Dysbiosis and Seizure Control Recruiting NCT04705298 Phase 4
26 FEcal Transplant, a Hope to Eradicate Colonization of Patient Harboring eXtreme Drug Resistant Bacteria? Recruiting NCT03029078 Phase 4 fecal microbiota transplant
27 An Open Label Study Evaluating the Safety and Efficacy of Switching From Rilpivirine/Emtricitabine/Tenofovir Alafenamide in Combination With Dolutegravir, to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Combination With Doravirine, in Male HIV+ Subjects > 45 Years With Multi-drug Resistant Virus and Virologic Suppression (Documented With at Least One Viral Load Result < 50 Copies Per mL) During the Last 6 Months on Current Therapy Active, not recruiting NCT04538040 Phase 4 Bictegravir/emtricitabine/tenofovir alafenamide + Doravirine switch
28 Clinical Management of Antiplatelet Drug Resistance in Patients With Drug Eluting Coronary Stents Withdrawn NCT00589862 Phase 4 Plavix (Clopidogrel)
29 ADRENL - ACTHAR Gel for Drug REsistant Nephrotic Syndrome in Children, Pilot Study Withdrawn NCT03408405 Phase 4 Acthar Gel 80 UNT/ML Injectable Solution
30 Effect of the Treatment of Vitamin D Deficiency in Drug-resistant Epilepsy Unknown status NCT03475225 Phase 3 Cholecalciferol;Placebo Oral
31 Colistin Plus Fosfomycin in Multi-Drug Resistant Acinetobacter Baumannii Unknown status NCT01297894 Phase 3 colistin;colistin plus fosfomycin
32 Polymyxin B Monotherapy Versus Polymyxin B-Carbapenem Combination Therapy in Critically Ill Patients With Multi-drug Resistant Gram-negative Infection: A Prospective, Parallel-Group, Double-Blind, Randomized Controlled Study Unknown status NCT03159078 Phase 3 Polymyxin B
33 Randomised, Open, Parallel Group Clinical Trial to Compare the Efficacy and Safety of a Single Dose of Ciprofloxacin Oral Suspension 20 Mg/Kg With a 3-Day Course of Erythromycin Oral Suspension Administered in a Dose of 12.5 Mg/Kg Every 6 Hours (12 Doses) in the Treatment of Children,With Clinically Severe Cholera Due to V. Cholerae O1 or O139. Completed NCT00142272 Phase 3 Ciprofloxacin
34 Anti-malarial Drug Resistance in Cameroon: Therapeutic Efficacy and Biological Markers of Resistance Completed NCT00146718 Phase 2, Phase 3 Amodiaquine and Sulphadoxine/Pyrimethamine
35 A Phase 3 Open-label Trial Assessing the Safety and Efficacy of Bedaquiline Plus PA-824 Plus Linezolid in Subjects With Pulmonary Infection of Either Extensively Drug-resistant Tuberculosis (XDR-TB) or Treatment Intolerant / Non-responsive Multi-drug Resistant Tuberculosis (MDR-TB). Completed NCT02333799 Phase 3 Bedaquiline;PA-824;Linezolid
36 Clinical Efficacy of Rifabutin in the Treatment of Serious and Life Threatening Infections Due to Mycobacterium Avium Complex, or Drug Resistant Mycobacterium Tuberculosis, or Other Drug Resistant Mycobacterium Completed NCT03164291 Phase 3 Rifabutin
37 A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Trial to Evaluate the Safety and Efficacy of Delamanid (OPC-67683) Administered Orally as 200 mg Total Daily Dose for Six Months in Patients With Pulmonary Sputum Culture-positive, Multidrug-resistant Tuberculosis Completed NCT01424670 Phase 3 Delamanid + OBR;Placebo + OBR
38 A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Padsevonil as Adjunctive Treatment of Focal-Onset Seizures in Adult Subjects With Drug-Resistant Epilepsy Completed NCT03739840 Phase 3 Padsevonil;Placebo
39 An Open-Label, Multicenter, Extension Study to Evaluate the Safety and Efficacy of Padsevonil as Adjunctive Treatment of Focal-Onset Seizures in Adult Subjects With Drug-Resistant Epilepsy Completed NCT03370120 Phase 2, Phase 3 Padsevonil
40 A Multicenter, Double Blind, Randomized, Placebo-Controlled Trial to Determine the Efficacy and Safety of Ganaxolone as Adjunctive Therapy for Adults With Drug-Resistant Partial-Onset Seizures Followed by Long-term Open-Label Treatment Completed NCT01963208 Phase 3 ganaxolone;Placebo
41 Assessment of Antimalaria Drugs Susceptibility Testing for an Effective Management of Infected Patients in Sub-Sahara Africa Completed NCT02974348 Phase 3 Arthemeter-lumefantrine;Artesunate mefloquine;Dihydroartemisinin piperaquine;Paracetamol;Amoxicillin;Quinine
42 A Multi-centre, Open-label Randomised Trial to Assess the Efficacy, Safety and Tolerability of Triple Artemisinin-based Combination Therapies (TACTs) Com-pared to Artemisinin-based Combination Therapies (ACTs) in Uncomplicated Falciparum Malaria and to Map the Geographical Spread of Artemisinin and Partner Drug Resistance Completed NCT02453308 Phase 2, Phase 3 ACT;TACT
43 Treating Malaria During Pregnancy: A Randomized Trial of Potential Options for Treatment in an Area of High Drug Resistance in Tanzania Completed NCT00146731 Phase 3 SP;SP + amodiaquine;AQ + artesunate;chlorproguanil-dapsone
44 Randomized Controlled Trial for the Treatment of Extensively Drug-Resistant Gram-negative Bacilli Completed NCT01597973 Phase 3 colistin and meropenem;colistin and placebo
45 A Phase 3, Multicenter, Expanded Access Study of Ibalizumab Plus an Optimized Background Regimen (OBR) in Treatment-Experienced Patients Infected With Multi-Drug Resistant (MDR) HIV-1 Completed NCT02707861 Phase 3 ibalizumab;Optimized Background Regimen
46 A Phase 3, Single Arm, 24-Week, Multicenter Study of Ibalizumab Plus an Optimized Background Regimen (OBR) in Treatment-Experienced Patients Infected With Multi-Drug Resistant HIV-1 Completed NCT02475629 Phase 3 Optimized Background Regimen (OBR)
47 A Phase 3 Open-Label Partially Randomized Trial to Evaluate the Efficacy, Safety and Tolerability of the Combination of Moxifloxacin Plus PA-824 Plus Pyrazinamide After 4 and 6 Months of Treatment in Adult Subjects With Drug-Sensitive Smear-Positive Pulmonary Tuberculosis and After 6 Months of Treatment in Adult Subjects With Multi-Drug Resistant, Smear-Positive Pulmonary Tuberculosis. Completed NCT02342886 Phase 3 Moxifloxacin;PA-824;Pyrazinamide;HRZE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol combination);HR (rifampicin plus isoniazid combination tablets)
48 Randomized, Open-label, Comparative Safety and Efficacy Study of Tipranavir Boosted With Low Dose Ritonavir (TPV/RTV) Versus Genotypically-defined Protease Inhibitor/Ritonavir (PI/RTV) in Multiple Antiretroviral Drug-experienced Patients (RESIST 2: Randomized Evaluation of Strategic Intervention in Multi-Drug Resistant Patients With Tipranavir) Completed NCT00144170 Phase 3 Tipranavir (with low dose ritonavir);Comparator protease inhibitor(CPI)/low dose ritonavir(r)
49 Impact of Cleansing With Chlorhexidine Gluconate (CHG) on Reducing Central Line Associated Bloodstream Infection (CLABSI) and Acquisition of Multi-drug Resistant Organisms (MDRO) in Children With Cancer or Those Receiving Allogeneic Hematopoietic Cell Transplantation (HCT) Completed NCT01817075 Phase 3
50 A Prospective Study of Shortening the Duration of Standard Short Course Chemotherapy From 6 Months to 4 Months in HIV-non-infected Patients With Fully Drug-Susceptible, Non-cavitary Pulmonary Tuberculosis With Negative Sputum Cultures After 2 Months of Anti-TB Treatment Completed NCT00130247 Phase 3 Ethambutol;Isoniazid;Pyrazinamide;Rifampin

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 VKORC1

Anatomical Context for Coumarin Resistance

MalaCards organs/tissues related to Coumarin Resistance:

40
Heart, Lung, Thyroid, Breast, Liver, Skin, Bone

Publications for Coumarin Resistance

Articles related to Coumarin Resistance:

(show top 50) (show all 222)
# Title Authors PMID Year
1
Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. 54 61 57 6
14765194 2004
2
Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements. 6 57
20555338 2010
3
VKORC1 polymorphisms, haplotypes and haplotype groups on warfarin dose among African-Americans and European-Americans. 57 6
18855533 2008
4
A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. 6 57
15888487 2005
5
The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes. 6 57
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 57
10961907 2000
9
Hereditary warfarin resistance. Investigation of a rare phenomenon. 57 61
3977518 1985
10
Warfarin resistance in the rat. 57 61
5671000 1968
11
Warfarin resistance. 57 61
6023007 1967
12
A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose. 57
19300499 2009
13
CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin dosing variability in the Italian population. 57
19207028 2009
14
Estimation of the warfarin dose with clinical and pharmacogenetic data. 57
19228618 2009
15
A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose. 57
18535201 2008
16
CYP4F2 genetic variant alters required warfarin dose. 57
18250228 2008
17
Pharmacogenomics--ready for prime time? 57
18322288 2008
18
Polymorphisms in the VKORC1 gene are strongly associated with warfarin dosage requirements in patients receiving anticoagulation. 6
16611750 2006
19
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. 57
16424822 2006
20
Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. 6
15805193 2005
21
CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis. 6
15714076 2005
22
Upstream and coding region CYP2C9 polymorphisms: correlation with warfarin dose and metabolism. 6
15608560 2004
23
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. 57
14656880 2004
24
Characterization of a novel CYP2A7/CYP2A6 hybrid allele (CYP2A6*12) that causes reduced CYP2A6 activity. 6
12325023 2002
25
Genetic polymorphism in exon 4 of cytochrome P450 CYP2C9 may be associated with warfarin sensitivity in Chinese patients. 6
11588061 2001
26
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
27
Characterisation and PCR-based detection of a CYP2A6 gene deletion found at a high frequency in a Chinese population. 6
10217419 1999
28
Genetic variation of CYP2A6, smoking, and risk of cancer. 6
10093988 1999
29
Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. 6
10208645 1999
30
Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. 6
10073515 1999
31
Genotyping of human cytochrome P450 2A6 (CYP2A6), a nicotine C-oxidase. 6
9827545 1998
32
Nicotine metabolism defect reduces smoking. 6
9655391 1998
33
Genetic association between sensitivity to warfarin and expression of CYP2C9*3. 6
9352571 1997
34
A single amino acid substitution (Leu160His) in cytochrome P450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin. 6
9409631 1997
35
The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. 6
8873220 1996
36
A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles. 6
7668294 1995
37
Molecular characterization of the murine Coh locus: an amino acid difference at position 117 confers high and low coumarin 7-hydroxylase activity in P450coh. 57
1302041 1992
38
The P450 superfamily: update on new sequences, gene mapping, and recommended nomenclature. 57
1991046 1991
39
Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. 57
646989 1978
40
Genetic variation between mice in their metabolism of coumarin and its derivatives. 57
566237 1978
41
Genetic variation in coumarin hydroxylase activity in the mouse (Mus musculus). 57
4366489 1974
42
The second reported kindred with hereditary resistance to oral anticoagulant drugs. 57
4192578 1970
43
Genetic control of dicumarol levels in man. 57
4177776 1968
44
Heritable resistance to warfarin in rats. 57
6049747 1967
45
HEREDITARY TRANSMISSION OF EXCEPTIONAL RESISTANCE TO COUMARIN ANTICOAGULANT DRUGS. THE FIRST REPORTED KINDRED. 57
14187664 1964
46
Pharmacodynamic resistance to warfarin is associated with nucleotide substitutions in VKORC1. 61 54
18680536 2008
47
A vitamin K epoxide reductase complex subunit 1 mutation in an Irish patient with warfarin resistance. 54 61
18266023 2008
48
[New insight in therapeutic anticoagulation by Coumarin derivatives]. 61 54
18278162 2008
49
VKORC1 and the vitamin K cycle. 54 61
18374188 2008
50
Current pharmacogenetic developments in oral anticoagulation therapy: the influence of variant VKORC1 and CYP2C9 alleles. 61 54
17849045 2007

Variations for Coumarin Resistance

ClinVar genetic disease variations for Coumarin Resistance:

6 (show all 28)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CYP2C9 NM_000771.4(CYP2C9):c.622T>G (p.Leu208Val) SNV Pathogenic 8410 rs72558191 GRCh37: 10:96707676-96707676
GRCh38: 10:94947919-94947919
2 VKORC1 NM_024006.6(VKORC1):c.85G>T (p.Val29Leu) SNV Pathogenic 2207 rs104894539 GRCh37: 16:31105966-31105966
GRCh38: 16:31094645-31094645
3 VKORC1 NM_024006.6(VKORC1):c.134T>C (p.Val45Ala) SNV Pathogenic 2208 rs104894540 GRCh37: 16:31105917-31105917
GRCh38: 16:31094596-31094596
4 VKORC1 NM_024006.6(VKORC1):c.172A>G (p.Arg58Gly) SNV Pathogenic 2209 rs104894541 GRCh37: 16:31105879-31105879
GRCh38: 16:31094558-31094558
5 VKORC1 NM_024006.6(VKORC1):c.196G>A (p.Val66Met) SNV Pathogenic 692018 rs72547529 GRCh37: 16:31104720-31104720
GRCh38: 16:31093399-31093399
6 VKORC1 NM_024006.6(VKORC1):c.106G>T (p.Asp36Tyr) SNV Pathogenic 2212 rs61742245 GRCh37: 16:31105945-31105945
GRCh38: 16:31094624-31094624
7 CYP2C9 CYP2C9*3 SNV drug response 8408 rs1057910 GRCh37: 10:96741053-96741053
GRCh38: 10:94981296-94981296
8 CYP2C9 CYP2C9*2 SNV drug response 8409 rs1799853 GRCh37: 10:96702047-96702047
GRCh38: 10:94942290-94942290
9 VKORC1 NM_024006.5(VKORC1):c.-226-1362dupG Duplication drug response 60671 rs397509427 GRCh37: 16:31107637-31107638
GRCh38: 16:31096316-31096317
10 APOE NM_000041.4(APOE):c.388T>C (p.Cys130Arg) SNV drug response 17864 rs429358 GRCh37: 19:45411941-45411941
GRCh38: 19:44908684-44908684
11 APOE NM_000041.2(APOE):c.526C>T (p.Arg176Cys) SNV drug response 17848 rs7412 GRCh37: 19:45412079-45412079
GRCh38: 19:44908822-44908822
12 VKORC1 NM_024006.6(VKORC1):c.383T>G (p.Leu128Arg) SNV drug response 2210 rs104894542 GRCh37: 16:31102564-31102564
GRCh38: 16:31091243-31091243
13 VKORC1 NM_024006.4(VKORC1):c.-1639G>A SNV drug response 2211 rs9923231 GRCh37: 16:31107689-31107689
GRCh38: 16:31096368-31096368
14 CYP2A6 NM_000762.5(CYP2A6):c.479T>A (p.Leu160His) SNV drug response 16969 rs1801272 GRCh37: 19:41354533-41354533
GRCh38: 19:40848628-40848628
15 overlap with 3 genes CYP2A6*12A Deletion drug response 16973 GRCh37: 19:41354669-41387493
GRCh38: 19:40848764-40881588
16 VKORC1 NM_024006.6(VKORC1):c.174-136C>T SNV drug response 37344 rs9934438 GRCh37: 16:31104878-31104878
GRCh38: 16:31093557-31093557
17 CYP2C9 NM_000771.4(CYP2C9):c.1075= (p.Ile359=) SNV drug response 163020 rs1057910 GRCh37: 10:96741053-96741053
GRCh38: 10:94981296-94981296
18 CYP2C9 CYP2C9*3 SNV drug response 163021 rs1057910 GRCh37: 10:96741053-96741053
GRCh38: 10:94981296-94981296
19 VKORC1 NM_024006.5(VKORC1):c.-226-1413G= SNV drug response 166563 rs9923231 GRCh37: 16:31107689-31107689
GRCh38: 16:31096368-31096368
20 CYP2C9 CYP2C9*2 SNV drug response 177709 rs1799853 GRCh37: 10:96702047-96702047
GRCh38: 10:94942290-94942290
21 APOB NM_000384.3(APOB):c.13013G>A (p.Ser4338Asn) SNV drug response 128418 GRCh37: 2:21225281-21225281
GRCh38: 2:21002409-21002409
22 APOB NM_000384.3(APOB):c.1853C>T (p.Ala618Val) SNV drug response 128420 GRCh37: 2:21250914-21250914
GRCh38: 2:21028042-21028042
23 APOB NM_000384.3(APOB):c.1594C>T (p.Arg532Trp) SNV drug response 255979 GRCh37: 2:21252534-21252534
GRCh38: 2:21029662-21029662
24 APOB NM_000384.3(APOB):c.293C>T (p.Thr98Ile) SNV drug response 128422 GRCh37: 2:21263900-21263900
GRCh38: 2:21041028-21041028
25 APOB NM_000384.3(APOB):c.7545C>T (p.Thr2515=) SNV drug response 128425 rs693 GRCh37: 2:21232195-21232195
GRCh38: 2:21009323-21009323
26 APOE NC_000019.9:g.45408836T>G SNV drug response 619951 rs405509 GRCh37: 19:45408836-45408836
GRCh38: 19:44905579-44905579
27 APOE NM_000041.4(APOE):c.43+520G>A SNV drug response 619952 rs769450 GRCh37: 19:45410444-45410444
GRCh38: 19:44907187-44907187
28 APOE NC_000019.9:g.45414451T>C SNV drug response 619953 rs439401 GRCh37: 19:45414451-45414451
GRCh38: 19:44911194-44911194

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

72 (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:

(show all 27)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
14.01 VKORC1L1 VKORC1 GGCX EPHX1 CYP4F2 CYP3A5
2
Show member pathways
13.1 EPHX1 CYP4F2 CYP3A5 CYP2D6 CYP2C9 CYP2C19
3
Show member pathways
12.76 EPHX1 CYP3A5 CYP2D6 CYP2C9 CYP2C19 CYP2C18
4
Show member pathways
12.22 VKORC1L1 VKORC1 APOE APOB
5 11.9 CYP2D6 CYP2C9 CYP2C19 CYP2C18
6
Show member pathways
11.86 CYP4F2 CYP2C9 CYP2C19
7
Show member pathways
11.86 PROZ GGCX F9 F2
8
Show member pathways
11.86 CYP3A5 CYP2D6 CYP2C9 CYP2C19 CYP2C18
9
Show member pathways
11.81 CYP3A5 CYP2D6 CYP2C9 CYP2C19 CYP2C18
10
Show member pathways
11.67 EPHX1 CYP2D6 CYP2A6
11
Show member pathways
11.52 CYP2D6 CYP2C9 CYP2C19
12
Show member pathways
11.48 CYP3A5 CYP2C9 CYP2C19
13
Show member pathways
11.47 CYP4F2 CYP3A5 CYP2D6 CYP2C9
14 11.44 F2 CYP3A5 CYP2C9 CYP2C19
15 11.31 CYP2D6 CYP2C19 APOE
16
Show member pathways
11.28 CYP3A5 CYP2D6 CYP2C9
17
Show member pathways
11.24 EPHX1 CYP3A5 CYP2D6 CYP2C9 CYP2C19 CYP2A6
18
Show member pathways
11.15 CYP3A5 CYP2D6 CYP2C9 CYP2C19
19
Show member pathways
11.14 CYP3A5 CYP2D6 CYP2C9 CYP2C19 CYP2A6
20 11.07 EPHX1 CYP2C9 CYP2A6
21 11.06 CYP3A5 CYP2C9 CYP2C19 CYP2A6
22 10.93 CYP2C9 CYP2A6
23
Show member pathways
10.93 CYP2C9 CYP2A6
24 10.79 CYP2D6 CYP2A6
25 10.79 CYP2D6 CYP2C19
26
Show member pathways
10.65 CYP2D6 CYP2C9
27 10.4 VKORC1 PROZ GGCX F9 F2 EPHX1

GO Terms for Coumarin Resistance

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

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 intracellular membrane-bounded organelle GO:0043231 10 VKORC1 PPIG EPHX1 CYP4F2 CYP3A5 CYP2D6
2 endoplasmic reticulum GO:0005783 9.83 VKORC1L1 VKORC1 MCFD2 GGCX EPHX1 CYP4F2
3 endoplasmic reticulum lumen GO:0005788 9.8 PROZ F9 F2 CALU APOE APOB
4 organelle membrane GO:0031090 9.76 EPHX1 CYP4F2 CYP3A5 CYP2D6 CYP2C9 CYP2C19
5 Golgi lumen GO:0005796 9.63 PROZ F9 F2
6 very-low-density lipoprotein particle GO:0034361 9.49