Study of Genetic Factors Other Than CYP2C9 and VKORC1 That Influence Warfarin Dose Requirements in a South-east Asian Population

Warfarin is a commonly used anti-coagulant, but has a narrow therapeutic index and wide inter-individual and inter-ethnic variation in dose requirements. Several genetic and non-genetic factors have been identified that could influence warfarin dose requirements. However, current known predictive factors could only explain about 50-60% of warfarin dose variability. Inter-ethnic differences in genetic influences on warfarin dose requirements also exist. We hypothesize that genetic factors other than CYP2C9 and VKORC1 may influence warfarin dosing and serve to further optimize warfarin dosing.

Inclusion Criteria:

• patients receiving maintenance warfarin therapy with a stable therapeutic international normalized ratio (INR) between 2 and 3 for at least 3 months,
• patients recruited from the anticoagulation clinics at the National University Hospital and Tan Tock Seng Hospital in Singapore between June 2002 and June 2004 for a previous genotyping study (C/00/510, NUH; C/00/535, TTSH, PI-Dr Goh Boon Cher).

Exclusion Criteria:

• patients below 21 years old, or
• patients with liver disease, malabsorption or chronic diarrheal diseases, or
• patients taking drugs that may potentially interact with warfarin.

Dietary advice to avoid foods that may interfere with warfarin pharmacokinetics will be given to patients during warfarin therapy.