Clinical Applications of Pharmacogenomics of Warfarin

Abstract

Various aspects of warfarin pharmacogenomics from marker discovery to clinical implementation were explored in the Singaporean context. Firstly, CYP4F2 V433M was found to have a small but significant effect on warfarin maintenance dose (WMD), but not GGCX and EPHX1. Next, genetic factors (CYP2C9, VKORC1 and CYP4F2) were shown to provide additional predictive information towards WMD, demonstrating that ethnicity is not a sufficient surrogate for genetic information. Assessment of the population impact of warfarin pharmacogenetic testing (WPGT) using the population attributable fraction then found that Whites are likely to benefit from genotyping while Blacks, Japanese and Chinese may not, highlighting the need to study the benefits of WPGT in different races more carefully. Lastly, Singaporean Chinese were surveyed for their attitudes, preferences and willingness-to-pay (WTP) for WPGT, and the findings suggest that patient acceptance is unlikely to be a major barrier, and WPGT is likely to be economically sustainable.