CYP2C9 and VKORC1 Polymorphisms Are Differently Distributed in the Brazilian Population According to Self-Declared Ethnicity or Genetic Ancestry

Autor(es)

Gadi Soares, Renata Alonso ^[1] ; Junior Lima Santos, Paulo Caleb ^[1] ; Lins Machado-Coelho, George Luiz ^[2] ; do Nascimento, Raimundo Marques ^[2] ; Mill, Jose Geraldo ^[3] ; Krieger, Jose Eduardo ^[1] ; Pereira, Alexandre Costa ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Heart Inst InCor, Lab Genet & Mol Cardiol, BR-05403000 Sao Paulo - Brazil

^[2] Univ Fed Ouro Preto, Dept Med, Ouro Preto, MG - Brazil

^[3] Univ Fed Espirito Santo, Dept Physiol, Vitoria, ES - Spain

• Tipo de documento: Artigo Científico
• Fonte: GENETIC TESTING AND MOLECULAR BIOMARKERS; v. 16, n. 8, p. 957-963, AUG 2012.
• Citações Web of Science: 17

Resumo

Background: Warfarin-dosing pharmacogenetic algorithms have presented different performances across ethnicities, and the impact in admixed populations is not fully known. Aims: To evaluate the CYP2C9 and VKORC1 polymorphisms and warfarin-predicted metabolic phenotypes according to both self-declared ethnicity and genetic ancestry in a Brazilian general population plus Amerindian groups. Methods: Two hundred twenty-two Amerindians (Tupinikin and Guarani) were enrolled and 1038 individuals from the Brazilian general population who were self-declared as White, Intermediate (Brown, Pardo in Portuguese), or Black. Samples of 274 Brazilian subjects from Sao Paulo were analyzed for genetic ancestry using an Affymetrix 6.0 (R) genotyping platform. The CYP2C9{*}2 (rs1799853), CYP2C9{*}3 (rs1057910), and VKORC1 g.-1639G>A (rs9923231) polymorphisms were genotyped in all studied individuals. Results: The allelic frequency for the VKORC1 polymorphism was differently distributed according to self-declared ethnicity: White (50.5%), Intermediate (46.0%), Black (39.3%), Tupinikin (40.1%), and Guarani (37.3%) (p < 0.001), respectively. The frequency of intermediate plus poor metabolizers (IM + PM) was higher in White (28.3%) than in Intermediate (22.7%), Black (20.5%), Tupinikin (12.9%), and Guarani (5.3%), (p < 0.001). For the samples with determined ancestry, subjects carrying the GG genotype for the VKORC1 had higher African ancestry and lower European ancestry (0.14 +/- 0.02 and 0.62 +/- 0.02) than in subjects carrying AA (0.05 +/- 0.01 and 0.73 +/- 0.03) (p = 0.009 and 0.03, respectively). Subjects classified as IM + PM had lower African ancestry (0.08 +/- 0.01) than extensive metabolizers (0.12 +/- 0.01) (p = 0.02). Conclusions: The CYP2C9 and VKORC1 polymorphisms are differently distributed according to self-declared ethnicity or genetic ancestry in the Brazilian general population plus Amerindians. This information is an initial step toward clinical pharmacogenetic implementation, and it could be very useful in strategic planning aiming at an individual therapeutic approach and an adverse drug effect profile prediction in an admixed population. (AU)

• Processo FAPESP: 10/17465-8 - Análise farmacogenética em pacientes tratados com fármacos do sistema cardiovascular e em indivíduos da população geral brasileira
• Beneficiário: Paulo Caleb Júnior de Lima Santos
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 10/17881-1 - Avaliação farmacogenética para os genes CYP2C9 e VKORC1 em pacientes usuários de varfarina e em indivíduos da população geral brasileira
• Beneficiário: Renata Alonso Gadi Soares
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica