Influence of APOE genotypes and VKORC1 haplotypes on warfarin dose requirements in Asian patients

Aims

To investigate the influence of APOE genotypes and VKORC1 haplotypes on warfarin dose requirements in Asian patients.

Methods

A total of 174 Asian patients (Chinese, n = 96; Malays, n = 50; Indians, n = 28) who had stable daily warfarin doses for at least 1 month were recruited. Following genomic DNA extraction from venous blood, pharmacogenetic analysis of APOE and VKORC1 genes was done by DNA sequencing.

Results

The majority of the Asian patients (78%) harboured the APOE ε3/ε3 genotype. Different APOE genotypes were found not to have any significant influence on mean daily warfarin dose requirements. Warfarin dose requirements in the pooled Asian patients homozygous for the VKORC1 H1 haplotype were significantly lower compared with patients homozygous for the H7 haplotype (H1-H1 vs. H7-H7: 2.79 ± 1.06 mg day⁻¹vs. 5.45 ± 2.3 mg day⁻¹, P < 0.001).

Conclusions

The present study suggests that APOE variants have minimal impact on warfarin dose requirements in Asian patients, probably due to the low frequency of ε4 allele containing genotypes.

What is already known about this subject

• Recent studies on pharmacogenetics of warfarin have implicated apolipoproteinE (APOE) polymorphisms to influence the vitamin K dependent coagulation cascade and hence the efficacy of warfarin.
• Studies among Caucasian and African Americans showed a significant but conflicting role of apolipoproteinE (APOE) isoforms in warfarin pharmacogenetics.
• The contribution of APOE isoforms in influencing variations in warfarin requirements in Asian subjects remains to be investigated.

What this study adds

• This is the first report of a population study in Asians exploring the role of isoforms encoded by three APOE alleles (ε2, ε3, ε4) in influencing warfarin dose requirements.
• The present study showed that the APOE ε3/ε3 isoform is the predominant genotype in the Asian population.
• The study also showed that APOE isoforms may not be important in affecting warfarin pharmacodynamics in Asian patients. It also suggested that the impact of different APOE isoforms depended on the frequency of APOE genotypes in the population, in particular the ε4 allele containing genotypes.

     

Management of Chinese patients on warfarin therapy in two models of anticoagulation service - a prospective randomized trial

AIM: To compare the treatment outcomes of a clinical pharmacist-managed anticoagulation service with physician-managed service in Chinese patients. METHODS: A prospective, randomized clinical trial was conducted at the anticoagulation clinic of a teaching hospital in Hong Kong. Patients aged > or = 18 years who would required warfarin therapy for at least 3 months were recruited. Patients were randomized to the pharmacist-managed or physician-managed group. Primary clinical outcome was assessed by the percentage of patient time spent within the target international normalized ratio (INR) range. The incidence of major thromboembolic events (TEs) and major bleeding was assessed as secondary clinical outcomes. The cost per patient per month (cPPPM) was calculated and patient satisfaction was assessed by patient satisfaction questionnaire (PSQ)-18. RESULTS: One hundred and forty-one patients were recruited at the anticoagulation clinic and 137 patients completed the study. Patients in the pharmacist-managed group (n = 68) were in the target INR 64% of patient time vs. 59% in the physician-managed group (n = 69) (P < 0.001). There was no significant difference in incidence of major TEs or bleeding. The cPPPM in the pharmacist-managed group (76 +/- 95 US dollar) (43 +/- 53 British pound) was lower than in the physician-managed group (98 +/- 158 US dollar) (55 +/- 89 British pound) (P < 0.001). The PSQ-18 score of the pharmacist-managed group (3.8 +/- 0.2) was higher than that of the physician-managed group (3.6 +/- 0.3) (P < 0.001). CONCLUSION: The pharmacist-managed anticoagulation service was more effective and less costly than the physician-managed service in achieving target anticoagulation control for Chinese patients on warfarin therapy.