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Aims: The aim of this study was to investigate the association between VKORC1 and CYP2C9 genes polymorphisms and the maintenance dose of warfarin in Peruvian patients.

Methods: An observational study was conducted on outpatients from the Hospital Grau ESSALUD in Lima, Peru. The participants were selected using nonprobabilistic convenience sampling. Inclusion criteria required patients to have been on anticoagulation therapy for >3 months, maintain stable doses of warfarin (consistent dose for at least 3 outpatient visits), and maintain an international normalized ratio within the therapeutic range of 2.5-3.5. DNA samples were obtained from peripheral blood for gene analysis.

Results: Seventy patients (mean age of 69.6 ± 13.4 years, 45.7% female) were included in the study. The average weekly warfarin dose was 31.6 ± 15.2 mg. The genotypic frequencies of VKORC1 were as follows: 7.1% (95% confidence interval, 2.4-15.9) for AA; 44.3% (32.4-56.7) for GA; and 48.6% (36.4-60.8) for GG. No deviation from the Hardy-Weinberg equilibrium was observed in the variants studied (P = .56). The mean weekly warfarin doses for AA, GA and GG genotypes were 16.5 ± 2.9, 26.5 ± 9.5 and 37.9 ± 17.1 mg, respectively (P < .001). The genotypic frequencies of CYP2C9 were as follows: 82.8% (72.0-90.8) for CC (*1/*1); 4.3% (1.0-12.0) for CT (*1/*2); and 12.9% (6.1-23.0) for TT (*2/*2). We did not find a significant association between the CYP2C9 gene polymorphism and the dose of warfarin.

Conclusions: The AA genotype of the VKORC1 gene was associated with a lower maintenance dose of warfarin in Peruvian patients.

Titel:	Association between polymorphisms of the VKORC1 and CYP2C9 genes and warfarin maintenance dose in Peruvian patients.
Autor/in / Beteiligte Person:	Oscanoa, TJ ; Guevara-Fujita, ML ; Fujita, RM ; Muñoz-Paredes, MY ; Acosta, O ; Romero-Ortuño, R
Link:	Zum Volltext
Zeitschrift:	British journal of clinical pharmacology, Jg. 90 (2024-03-01), Heft 3, S. 769-775
Veröffentlichung:	Oxford : Wiley-Blackwell ; <i>Original Publication</i>: London, Macmillan Journals Ltd., 2024
Medientyp:	academicJournal
ISSN:	1365-2125 (electronic)
DOI:	10.1111/bcp.15958
Schlagwort:	Humans Female Middle Aged Aged Aged, 80 and over Male Cytochrome P-450 CYP2C9 genetics Peru Vitamin K Epoxide Reductases genetics Polymorphism, Genetic Genotype International Normalized Ratio Warfarin Anticoagulants adverse effects
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Observational Study; Journal Article; Research Support, Non-U.S. Gov't Language: English [Br J Clin Pharmacol] 2024 Mar; Vol. 90 (3), pp. 769-775. <i>Date of Electronic Publication: </i>2023 Nov 24. MeSH Terms: Warfarin* ; Anticoagulants* / adverse effects ; Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Male ; Cytochrome P-450 CYP2C9 / genetics ; Peru ; Vitamin K Epoxide Reductases / genetics ; Polymorphism, Genetic ; Genotype ; International Normalized Ratio References: He Y, Wong ICK, Li X, et al. The association between non-vitamin K antagonist oral anticoagulants and gastrointestinal bleeding: a meta-analysis of observational studies. Br J Clin Pharmacol. 2016;82(1):285-300. doi:10.1111/bcp.12911. ; Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ETTL. New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. 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Grant Information: 54-IETSI-ESSALUD-2017 Kaelin Award, Instituto de Evaluación e Investigación de Tecnologías de la Salud-IETSI Contributed Indexing: Keywords: VKORC1; anticoagulation; international normalized ratio; pharmacogenetics; warfarin Substance Nomenclature: 5Q7ZVV76EI (Warfarin) ; EC 1.14.13.- (Cytochrome P-450 CYP2C9) ; 0 (Anticoagulants) ; EC 1.17.4.4 (Vitamin K Epoxide Reductases) ; EC 1.14.13.- (CYP2C9 protein, human) ; EC 1.17.4.4 (VKORC1 protein, human) Entry Date(s): Date Created: 20231108 Date Completed: 20240229 Latest Revision: 20240305 Update Code: 20240305

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Association between polymorphisms of the VKORC1 and CYP2C9 genes and warfarin maintenance dose in Peruvian patients.