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Distribution and Impact of CYP2C9, CYP2C19, and VKORC1 Genotypes on Acenocoumarol Dose Requirements in Elderly Patients
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Abstract
Objective: To investigate the distribution of CYP2C9, CYP2C19, and VKORC1 genotypes in elderly Vietnamese patients and to evaluate their associations with the maintenance dose of acenocoumarol required to achieve the target international normalized ratio (INR). Methods: A descriptive cross-sectional study was conducted at 30-4 Hospital, Ministry of Public Security, from January 2023 to January 2025. A total of 187 patients aged ≥60 years who were receiving stable acenocoumarol therapy were genotyped for CYP2C9 (*2, *3), CYP2C19 (*2, *3), and VKORC1 (-1639G>A). The mean weekly dose of acenocoumarol was compared across individual genotypes and combinations of two or three genes. Results: The distribution of genotypes was as follows: CYP2C9 *1/*1 (95%), VKORC1 AA (66%), and ≥1 reduced-function CYP2C19 allele (55%). Patients with CYP2C9 *1/*1 required a significantly higher dose than those with *2/*3 genotypes (10.63 ± 3.28 vs. 7.48 ± 3.17 mg/week; p = 0.011). VKORC1 AA carriers required significantly lower doses than GA or GG carriers (p < 0.001). No statistically significant difference was observed for CYP2C19 genotypes. The lowest dose among two-gene combinations was found in *2/*3 + VKORC1 AA, while the highest was in *1/*1 + VKORC1 GG. Among three-gene combinations, *2/*3 + AA + *1/*1 required the lowest dose and *1/*1 + GG + *2/*2 the highest. Conclusion: CYP2C9 and VKORC1 polymorphisms significantly influence acenocoumarol dose requirements in elderly patients. Pharmacogenetic testing of these variants may support personalized anticoagulation therapy in this population.
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Keywords
Acenocoumarol, CYP2C9, CYP2C19, VKORC1, elderly patients, CYP2C9
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