Mean Stable Warfarin Doses Versus CYP2C9*2 and VKORC11639G>A Genotypes in Sudanese Population

Abstract

Warfarin is a potent anticoagulant with a confirmed effectiveness when anticoagulation targets are attained, an issue, that is troublesome to reach due to the fact that warfarin has a narrow therapeutic index (NTI), that means they have a narrow window between their effective doses and those at which they produce adverse toxic effects. However, oral anticoagulation throughout genetics recommended a genotype guided dosing, but is it favourable over clinical based dosing? Objectives: To analyze the mean stable warfarin doses attained clinically within CYP2C9*2 and VKORC11639G>A wild-type and variant genotype status in Sudanese patients. Method: Genotyping for the CYP2C9*2 and VKORC1-1639G>A polymorphisms were accomplished with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) technique. The mean stable warfarin dose per genotype was defined as the mean stable warfarin dose related to the stable INR within target range within a genotype of each of CYP2C9*2 or VKORC11639G> Agenes, using Analysis of Variance (ANOVA) as the statistical method. Results: Fifty-three stable patients with wild-type CYP2C9*1*1 genotype had a mean stable warfarin dose of 4.9 ± 2.1 mg, 5 patients who were heterozygous CYP2C9*1*2 genotype, had a mean stable warfarin dose of 5.0 ± 0.71mg, and 2 patients were homozygous mutant CYP2CP*2*2 genotype had a mean stable warfarin dose of 4.8 ± 0.3 mg. The results were statistically insignificant, P = 0.992.Sixteen unstable patients were of wild-type CYP2C9*1*1 genotype, 40 patients with heterozygous CYP2C9*1*2 genotype, and 4 with homozygous mutant CYP2CP*2*2 genotype, had mean stable doses of 5.32 ± 2.9, 6.5 ± 2.7 and 4.5 ± 0.71 mg respectively. The result was statistically insignificant, P = 0.508. Fifty-two stable patients were having wild-type VKORC1G/G genotype, 3 patients had heterozygous VKORC1G/A genotype and 3 patients had homozygous mutant VKORC1/AA genotype, these patients had mean stable doses of 5.41 ± 1.63, 4.8 ± 2.19 and 5.4 ± 0.99 mg respectively. The mean warfarin stable dose among homozygous mutant VKORC1A/A genotype was lower than among wild-type and heterozygous genotype profiles. This result was statistically not significant, P = 0.729.In the unstable group, 8 patients of wild-type VKORC1G/G genotype, had a mean stable warfarin dose of 7.34 ± 3.9 mg, 40 patients of heterozygous VKORC1G/A genotype had a mean stable warfarin dose of 5.21 ± 2.76 mg, and 10 patients of homozygous VKORC1A/A genotype had a mean stable warfarin dose of 4.3 ± 1.83 mg. The result was statistically insignificant, P = 0.067.Conclusion: In our study, as there were no significant differences between warfarin mean stable doses related to different CYP2C9*2 and VKORC11639G>A genotypes, the evidence is not satisfactory to conclude that the conventional use of genotype guided warfarin dosing will correct stable warfarin dose among Sudanese patients.