OBJECTIVETo evaluate the effect of VKORC1, CYP2C9, GGCX, PROC, EPHX1 and CYP4F2 gene polymorphisms on Warfarin maintenance dose variation in Chinese Han Population.

METHODSFour hundred eighty-eight patients with prosthetic heart valves, atrial fibrillation or pulmonary thromboembolism and achieved stable Warfarin dose were enrolled. TaqMan probe or direct sequencing were used to genotype Y9VKORC1, CYP2C9, GGCX, EPHX1 and CYP4F2 gene polymorphisms. Demographic characteristics, stable therapeutic dose of Warfarin and concomitant medications were collected for all patients. The effect of VKORC1, CYP2C9, GGCX, PROC, EPHX1 and CYP4F2 gene polymorphisms, demographic characteristics and concomitant medications on Warfarin daily maintenance dose were analyzed with statistical method.

RESULTSVKORC1 and CYP2C9 gene polymorphisms could explain more than 50% Warfarin maintenance dose variation in recruited patients, while CYP4F2 gene polymorphisms could only explain 1%. GGCX, PROC and EPHX1 gene polymorphisms had no impact no Warfarin maintenance dose. VKORC1 and CYP2C9 gene polymorphisms have a greater impact on Warfarin maintenance dose compared with demographic characteristics and concomitant medications.

CONCLUSIONVKORC1 and CYP2C9 gene polymorphisms have a significant impact on Warfarin maintenance dose in Chinese Han population.

Adult ; Aged ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; ethnology ; genetics ; Atrial Fibrillation ; drug therapy ; ethnology ; genetics ; Cytochrome P-450 CYP2C9 ; Cytochrome P-450 Enzyme System ; genetics ; Cytochrome P450 Family 4 ; Dose-Response Relationship, Drug ; Epoxide Hydrolases ; genetics ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Protein C ; genetics ; Pulmonary Embolism ; drug therapy ; ethnology ; genetics ; Treatment Outcome ; Vitamin K Epoxide Reductases ; genetics ; Warfarin ; administration & dosage ; Young Adult

No abstract available.
Aged ; Anticoagulants/therapeutic use ; DNA Mutational Analysis ; Echocardiography ; Genetic Predisposition to Disease ; Homozygote ; Humans ; Hyperhomocysteinemia/blood/complications/diagnosis/drug therapy/*genetics ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/*genetics ; *Mutation ; Phenotype ; Pulmonary Embolism/blood/diagnosis/drug therapy/*etiology ; Severity of Illness Index ; Thrombolytic Therapy ; Tomography, X-Ray Computed ; Treatment Outcome ; Vitamins/therapeutic use

Pharmacogenetic testing for clinical applications is steadily increasing. Correct and adequate use of pharmacogenetic tests is important to reduce unnecessary medical costs and adverse patient outcomes. This document contains recommended pharmacogenetic testing guidelines for clinical application, interpretation, and result reporting through a literature review and evidence-based expert opinions for the clinical pharmacogenetic testing covered by public medical insurance in Korea. This document aims to improve the utility of pharmacogenetic testing in routine clinical settings.
Anticoagulants/therapeutic use ; Antidepressive Agents/therapeutic use ; Antimetabolites, Antineoplastic/therapeutic use ; Antitubercular Agents/therapeutic use ; Arylamine N-Acetyltransferase/genetics ; Coronary Artery Disease/drug therapy/genetics ; Cytochrome P-450 CYP2C19/genetics ; Cytochrome P-450 CYP2C9/genetics ; Cytochrome P-450 CYP2D6/genetics ; Depressive Disorder/drug therapy/genetics ; Genotype ; Isoniazid/therapeutic use ; Laboratories, Hospital/standards ; Methyltransferases/genetics ; Pharmacogenomic Testing/*methods/standards ; Platelet Aggregation Inhibitors/therapeutic use ; Pulmonary Embolism/drug therapy/genetics ; Ticlopidine/analogs & derivatives/therapeutic use ; Tuberculosis/drug therapy/genetics ; Vitamin K Epoxide Reductases/genetics ; Warfarin/therapeutic use

The incidence of pulmonary embolism (PE) rises markedly with age, and only a few cases have been reported in younger adults. Thrombophilia has been reported as one of the predisposing factors for PE in younger adults. Here we report an extraordinary case of PE complicated with dysplasminogenemia, a rare genetic disorder resulting in hypercoagulability, in a young male. An 18-yr-old male visited an emergency room in the United States complaining chest discomfort. He was diagnosed as PE with deep vein thrombosis without apparent risk factors. Anticoagulation therapy with warfarin had been initiated and discontinued after 6 months of treatment. After returning to Korea he was tested for thrombophilia which revealed decreased activity of plasminogen and subsequent analysis of PLG gene showed heterozygous Ala620Thr mutation. He was diagnosed with PE complicated with dysplasminogenemia. Life-long anticoagulation therapy was initiated. He is currently under follow-up without clinical events for 2 yr.
Acute Disease ; Adolescent ; Anticoagulants/therapeutic use ; Conjunctivitis/complications/*diagnosis ; Heterozygote ; Humans ; Male ; Plasminogen/*deficiency/genetics ; Polymorphism, Single Nucleotide ; Pulmonary Embolism/*diagnosis/drug therapy/etiology ; Risk Factors ; Skin Diseases, Genetic/complications/*diagnosis ; Tomography, X-Ray Computed ; Venous Thrombosis/etiology ; Warfarin/therapeutic use