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Warfarin is commonly used as an oral anticoagulant to treat or prevent abnormal blood clotting. The effective daily dose of the drug varies widely in different individuals, and at present has to be established by trial and error. Higher-than-optimal doses of warfarin can lead to bleeding complications. The metabolism of the drug involves a cytochrome P450 enzyme, CYP2C9; two allelic variants of the CYP2C9 gene (CYP2C9*2 and CYP2C9*3) break down warfarin at a substantially lower rate than the wild-type CYP2C9*1 allele. Aithal et al. [Lancet (1999) 353, 717-719 (Abstract); also see Editorial by Mannucci on p. 688] report that, in patients requiring anticoagulant therapy, those who required a low dose of warfarin were about six times more likely to have one or two slow-metaboliser alleles of CYP2C9. These people were also more likely to have bleeding complications, and to experience problems in establishing the correct dose of warfarin.

Comment: This paper is flagged in the journal as an 'Early Report'. Although the overall result seems robust, the confidence intervals are large so the true magnitude of the effect needs confirmation. If it is confirmed, further studies will be required to establish the cost-effectiveness of genotyping patients requiring anticoagulant treatment. About 20% of the population carries at least one of the mutant alleles, and knowing a patient's genotype in advance could avoid costly clinic and hospital time during the induction period, as well as potentially life-threatening complications.