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

Germline DNA will be genotyped for variants in genes in the anti-coagulation pathway, including CYP4F2, GGCX and EPHX1. The germline DNA was previously collected from a warfarin study (C/00/510, NUH, C/00/535, TTSH, PI-Dr Goh Boon Cher). Samples were anonymized, and data analysis will be done without patient identifiers. Germline DNA previously collected from 279 patients who were on maintenance warfarin dose will be genotyped.

The clinical data that has been collected and will be used for the study include: gender, race, age, body weight, maintenance warfarin dose, serum albumin, two consecutive stable INR values, and indications for warfarin use.

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.