Association of VKORC1 variants with stable acenocoumarol maintenance dose in Algerian patients: A single-center pharmacogenetic study

We hypothesized that VKORC1 genetic variation contributes to stable acenocoumarol maintenance-dose requirements in Algerian patients. This prospective single-center study included 119 of 321 adults assessed for eligibility in Sétif between November 2017 and September 2019. Eligible patients had received acenocoumarol for at least six months, maintained an indication-specific international normalized ratio within the therapeutic range for at least three months, and achieved a time in therapeutic range >60% according to the Rosendaal method. The stable maintenance dose was defined as the mean prescribed daily dose recorded during visits with therapeutic international normalized ratio values. VKORC1 rs9923231, rs7294, and rs17708472 were genotyped using polymerase chain reaction– restriction fragment length polymorphism. The mean maintenance dose was 3.08±1.60 mg/day. For rs9923231, the mean maintenance doses were 4.27, 3.42, and 2.11 mg/day in GG, GA, and AA genotype carriers, respectively. Compared with GG carriers, adjusted dose ratios were 0.87 (95% confidence interval [CI], 0.71-1.07) for GA and 0.53 (95% CI, 0.43-0.66) for AA (overall P < 0.001). The rs7294 variant was associated with a higher maintenance dose (dose ratio 1.18, 95% CI 1.05-1.34; Holm-adjusted P=0.016), whereas rs17708472 showed no independent association. These findings demonstrate that VKORC1 rs9923231 is a major determinant of stable acenocoumarol maintenance-dose requirements in this Algerian cohort, with the greatest dose reduction observed in AA homozygotes.