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

Br J Clin Pharmacol. 2023 Nov 8. doi: 10.1111/bcp.15958. Online ahead of print.

ABSTRACT

AIM: 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 non-probabilistic convenience sampling. Inclusion criteria required patients to have been on anticoagulation therapy for more than three months, maintain stable doses of warfarin (consistent dose for at least three outpatient visits), and maintain an INR 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% CI, 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=0.56). The mean weekly warfarin doses for AA, GA, and GG genotypes were 16.5 ± 2.9 mg, 26.5 ± 9.5 mg, and 37.9 ± 17.1 mg, respectively (p<0.001). 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.

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

PMID:37940132 | DOI:10.1111/bcp.15958