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APOE genotype makes a small contribution to warfarin dose requirements

Lookup NU author(s): Elizabeth Sconce, Emerita Professor Ann Daly, Dr Tayyaba Khan, Dr Hilary Wynne, Professor Farhad Kamali

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Abstract

Alterations in vitamin K availability can significantly influence anticoagulation response to warfarin. Apolipoprotein E (APOE) plays a part in the hepatic uptake of lipid-soluble vitamin K. This study aimed to determine the influence of common polymorphisms in the APOE gene on warfarin dose requirements. patients with stable anticoagulation control and with a target International Normalized Ratio (INR) 2.0-3.0 were genotyped for the APOE ε2, ε3 and ε4 variants. Mean±SD daily warfarin doses were significantly lower in patients carrying at least one ε4 allele compared to the ε3ε3 reference genotype (3.3±1.9 versus 4.0±1.8; P=0.03; 95% CI: 0.1-1.2). Multivariate regression analysis showed that patient age, height and CYP2C9, VKORC1 and APOE genotypes significantly contributed to warfarin dose requirement (R=57%). only the ε4 allele of APOE was found to make a significant (P=0.002) but small contribution to warfarin dose requirement. There was no significant difference in fasted plasma vitamin K concentration between patients with the different APOE genotypes. This study suggests that APOE genotype is unlikely to have a clinically significant effect on warfarin dose requirements. © 2006 Lippincott Williams & Wilkins.

Publication metadata

Author(s): Sconce EA, Daly AK, Khan TI, Wynne HA, Kamali F

Publication type: Article

Publication status: Published

Journal: Pharmacogenetics and Genomics

Year: 2006

Volume: 16

Issue: 8

Pages: 609-611

ISSN (print): 1744-6872

ISSN (electronic): 1744-6880

Publisher: Lippincott Williams & Wilkins

URL: http://dx.doi.org/10.1097/01.fpc.0000220567.98089.b5

DOI: 10.1097/01.fpc.0000220567.98089.b5

PubMed id: 16847429

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