1. Influence of APOE genotypes and VKORC1 haplotypes on warfarin dose requirements in Asian patients
- Author
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Lai-Heng Lee, Suman Lal, Boon Cher Goh, Edwin Sandanaraj, Soo-Chin Lee, Balram Chowbay, Srinivasa Rao Jada, and Ming-Chai Kong
- Subjects
Adult ,Apolipoprotein E ,Genotype ,Population ,Physiology ,Pharmacology ,Biology ,Mixed Function Oxygenases ,Apolipoproteins E ,Short Reports ,Asian People ,Vitamin K Epoxide Reductases ,medicine ,Humans ,Protein Isoforms ,Pharmacology (medical) ,education ,Aged ,Aged, 80 and over ,education.field_of_study ,Homozygote ,Warfarin ,Genetic Variation ,Middle Aged ,Vitamin-K-epoxide reductase (warfarin-sensitive) ,Haplotypes ,Population study ,Vitamin K epoxide reductase ,VKORC1 ,Pharmacogenetics ,medicine.drug - Abstract
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 (e2, e3, e4) in influencing warfarin dose requirements. • The present study showed that the APOE e3/e3 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 e4 allele containing genotypes. 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 e3/e3 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
- Published
- 2008
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