Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/198941
Type: Artigo de periódico
Title: Vkorc1 V66m Mutation In African Brazilian Patients Resistant To Oral Anticoagulant Therapy.
Author: Orsi, Fernanda A
Annichino Bizzacchi, Joyce M
de Paula, Erich V
Ozelo, Margareth C
Langley, Michael R
Weck, Karen E
Abstract: Warfarin-based anticoagulant therapy is associated with large variability in dose response. Genetic variability in the VKORC1 and CYP2C9 genes is associated with increased warfarin sensitivity. In addition, rare coding region mutations in VKORC1 have been associated with resistance to warfarin. VKORC1 and CYP2C9 variability associated with altered warfarin response is less well characterized in African and mixed-raced populations such as Brazilians. To determine genetic variability associated with altered warfarin response among Brazilian patients, sixty-two adult patients with extreme resistance or sensitivity to warfarin were genotyped for variants in CYP2C9 and VKORC1. Of the 51 patients on low doses of warfarin, the VKORC1--1639 (3673) G>A polymorphism associated with warfarin sensitivity was present in 48 (94.1%), including 97% of Caucasians, 82% of African-descent patients, and all 7 (100%) patients of Indian descent. Additionally, 52.9% of warfarin sensitive patients had at least one CYP2C9*2 or CYP2C9*3 decreased metabolism allele, 63.6% of Caucasians and 54% of African-descent patients. Of the 11 patients on high doses of warfarin, sequencing of VKORC1 revealed a nonsynonymous V66M mutation in two warfarin resistant patients, both of African-descent. Brazilian patients requiring low doses of warfarin have a high frequency of VKORC1 and CYP2C9 variants associated with warfarin sensitivity. The presence of the rare VKORC1 V66M in two warfarin high dose outlier patients implies that this variant may be more frequent among African Brazilians and has implications for future warfarin studies in other populations of African descent.
Subject: Administration, Oral
Adolescent
Adult
African Continental Ancestry Group
Aged
Aged, 80 And Over
Anticoagulants
Aryl Hydrocarbon Hydroxylases
Blood Coagulation
Brazil
Cytochrome P-450 Cyp2c9
Dose-response Relationship, Drug
Drug Resistance
Female
Gene Frequency
Haplotypes
Humans
Male
Middle Aged
Mixed Function Oxygenases
Mutation
Phenotype
Polymorphism, Genetic
Prospective Studies
Vitamin K Epoxide Reductases
Warfarin
Young Adult
Rights: fechado
Identifier DOI: 10.1016/j.thromres.2010.06.008
Address: http://www.ncbi.nlm.nih.gov/pubmed/20615525
Date Issue: 2010
Appears in Collections:Unicamp - Artigos e Outros Documentos

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