Association Between the Lower Extremity Deep Venous Thrombosis, the Warfarin Maintenance Dose, and CYP2C9*3, CYP2D6*10, and CYP3A5*3 Genetic Polymorphisms: A Case-Control Study

Autor: Yu Gao, Xiaofu Zhang, Feng-Tong Liu, Xin Cao, Cheng-Cheng Yan, Shang Ju
Rok vydání: 2017
Předmět:
Male
medicine.medical_specialty
CYP2D6
030204 cardiovascular system & hematology
Polymerase Chain Reaction
Polymorphism
Single Nucleotide

03 medical and health sciences
0302 clinical medicine
Gene Frequency
Internal medicine
medicine
Cytochrome P-450 CYP3A
Humans
International Normalized Ratio
CYP3A5
CYP2C9
Genetics (clinical)
Alleles
Genetic Association Studies
Aged
Cytochrome P-450 CYP2C9
Venous Thrombosis
biology
Dose-Response Relationship
Drug

Maintenance dose
business.industry
Warfarin
Case-control study
Anticoagulants
General Medicine
Middle Aged
medicine.disease
CYP2C9*3
Venous thrombosis
Cytochrome P-450 CYP2D6
Haplotypes
Lower Extremity
030220 oncology & carcinogenesis
Anesthesia
Case-Control Studies
Cardiology
biology.protein
Female
business
Polymorphism
Restriction Fragment Length

medicine.drug
Zdroj: Genetic testing and molecular biomarkers. 21(9)
ISSN: 1945-0257
Popis: This study explored the association between the CYP2C9*3/CYP2D6*10/CYP3A5*3 genetic polymorphisms with lower extremity deep venous thrombosis (LEDVT) and the warfarin maintenance dose.Five hundred thirty-six patients who were pathologically diagnosed with LEDVT after surgery were included in the LEDVT group. At the same time, 540 patients without LEDVT who underwent surgery were recruited as the control group. Patients were given warfarin at an initial dose of 2.5-3.0 mg. Blood samples were collected to detect the initial and stable international normalized ratio (INR) values. The warfarin maintenance dose was obtained if the INR remained within a range of 2.0-3.0 for 3 consecutive days. The genotype distribution and haplotype analysis of the CYP2C9*3/CYP2D6*10/CYP3A5*3 alleles were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) testing and SHEsis software, respectively. Logistic regression analysis was used to analyze the risk and protective factors for LEDVT.The A/G genotypes, G/G genotypes, and G allele of CYP3A5*3 in the LEDVT group were observed with increased frequency compared with the control group. The LEDVT group displayed a higher ACG haplotype frequency, and lower ACA and ATA haplotype frequencies than the control group. Age, diabetes, low-density lipoprotein, CYP3A5*3 and the ACG haplotype were independent risk factors for LEDVT. High-density lipoprotein and the ACA haplotype were independent protective factors for LEDVT. The genotype distributions of the CYP2C9*3, CYP2D6*10, and CYP3A5*3 genetic polymorphisms were associated with the warfarin maintenance dose.The CYP3A5*3 genetic polymorphism may be an important risk factor for LEDVT. Moreover, CYP2C9*3, CYP2D6*10, and CYP3A5*3 are associated with the warfarin maintenance dose.
Databáze: OpenAIRE