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Blood, 1 June 2002, Vol. 99, No. 11, pp. 4237-4239
BRIEF REPORT
Differential effects of 2C9*3 and
2C9*2 variants of cytochrome P-450
CYP2C9 on sensitivity to acenocoumarol
José Hermida,
José Zarza,
Ignacio Alberca,
Ramón Montes,
María Luz López,
Eva Molina, and
Eduardo Rocha
From the Hemostasis and Thrombosis Research Unit,
School of Medicine, University of Navarra, Pamplona,
Spain; the Haematology Service, University Clinic of
Navarra, Pamplona, Spain; and the Department of
Haematology, University Hospital of Salamanca, Spain.
The 2C9*3 and 2C9*2 polymorphisms of cytochrome P-450 CYP2C9 are
associated with hypersensitivity to warfarin and bleeding. The effect
of these polymorphisms on sensitivity to acenocoumarol is unknown.
Three groups of patients, with low, medium, or high acenocoumarol-dose
requirements, were studied. Age influenced the acenocoumarol
sensitivity. Bearing the 2C9*3 allele was associated with the need for
a lower acenocoumarol dose (odds ratio [OR], 6.02; 95% confidence
interval [CI], 1.50-24.18); 80% of carriers of the 2C9*3 allele
required a low dose. The 2C9*2 allele was associated with a lower
acenocoumarol-dose requirement (OR, 2.70; 95% CI, 1.11-6.58) because
of a reduced risk of the need for a high acenocoumarol dose (4.8% of
the patients in the high-dose group carried the 2C9*2 allele versus
34.1% and 30.2%, respectively, in the medium-dose and low-dose
groups). Therefore, carriers of 2C9*3 may need a low initial loading
dose of acenocoumarol. Because acenocoumarol sensitivity with the 2C9*2
variant does not seem to be clinically relevant, the drug could be an
alternative to warfarin in 2C9*2 carriers.
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