Abstract 2102

Poster Board II-79

BACKGROUND: Two enzymatic complexes are related to therapeutic response to coumarin: 1)cytocrome P-450 2C9 (CYP2C9), that metabolizes the drug; and 2)vitamin K epoxide reductase complex subunit 1 (VKORC1), targeted by coumarin. Haplotypes CYP2C9 *2 and *3 and VKORC1*2, more frequent in Caucasians, are related to coumarin sensitivity. VKORC1*3 and *4 confer resistance to the anticoagulant and are found mainly in Africandescents. MATERIAL AND METHODS: To determine genetic variability associated with altered warfarin response among Brazilian patients, sixty-two adult patients showing resistance or sensitivity to warfarin were genotyped for variants in CYP2C9 and VKORC1 associated with alteredwarfarin response. Fifty-one were users of low daily doses (¶ 2.5mg) and 11 users of high daily doses (>10mg) of warfarin.RESULTS: Among the 51 patients on low doses of warfarin, VKORC1 1639 (3673) G>A polymorphism, which defines VKORC1*2, was present in 48 (94.1%). Of these, thirty-two patients (66.7%) were Caucasians, 9 (18.7%) were of African descent, 4 (8.4%) were of both African and Brazilian-Indian descent and 3 (6.2%) were of Brazilian-Indian descent. Additionally, 27(52.9%) patients had at least one CYP2C9*2 or CYP2C9*3 allele, 21(63.6%) of Caucasians and 6 (54%) of African-descents. For the 11 patients on high doses of warfarin, 6 (54.5%) patients had at least one variant allele of VKORC1. Four patients were found with a non-coding VKORC1 polymorphism: VKOR3482(8773)C>T or VKOR 1173(6484)C>T. The VKOR 3482(8773)C>T, which defines the haplotype VKORC1*3F, was present in 2 African-descentpatients and VKOR 1173(6484)C>T, associated with VKORC1*2, was present in 3 patients. Two African-descent patients had a coding mutation Val66Met(V66M). CONCLUSION: The presence of the rare V66M mutation in two high dose outlier patients implies that this variant may be more frequent among African Brazilians and has implications for future warfarin studies in other individuals of African descent.

Disclosures:

No relevant conflicts of interest to declare.

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Asterisk with author names denotes non-ASH members.

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