Brazilian cohort and genes encoding for drug-metabolizing enzymes and drug transporters

Autor(es)

Kim, Vera ^{[1, 2]} ; van der Wal, Thijs ^[2] ; Nishi, Miriam Yumie ^[3] ; Montenegro, Luciana Ribeiro ^[3] ; Carrilho, Flair Jose ^[1] ; Hoshida, Yujin ^{[2, 4]} ; Ono, Suzane Kioko ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Dept Gastroenterol, Div Clin Gastroenterol & Hepatol, BR-05403000 Sao Paulo - Brazil

^[2] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, Tisch Canc Inst, Div Liver Dis, Dept Med, Liver Canc Program, New York, NY 10029 - USA

^[3] Univ Sao Paulo, Fac Med, Hosp Clin, Unidade Endocrinol Desenvolvimento, Disciplina End, BR-05403000 Sao Paulo - Brazil

^[4] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Simmons Comprehens Canc Ctr, Liver Tumor Transnat Res Program, Div Digest & Liv, Dallas, TX 75390 - USA

• Tipo de documento: Artigo Científico
• Fonte: PHARMACOGENOMICS; v. 21, n. 9, p. 575-586, JUN 2020.
• Citações Web of Science: 0

Resumo

Background \& aim: Genetic variability in drug absorption, distribution, metabolism and excretion (ADME) genes contributes to the high heterogeneity of drug responses. The present study investigated polymorphisms of ADME genes frequencies and compared the findings with populations from other continents, available in the 1000 Genome Project (1 KGP) and the Exome Aggregation Consortium (ExAC) databases. Methodology \& results: We conducted a study of 100 patients in Brazil and a total of 2003 SNPs were evaluated by targeted next-generation sequencing in 148 genes, including Phase I enzymes (n = 50), Phase II enzymes (n = 38) and drug transporters (n = 60). Overall, the distribution of minor allele frequency (MAF) suggests that the distribution of 2003 SNPs is similar between Brazilian cohort, 1 KGP and ExAC; however, we found moderate SNP allele-frequency divergence between Brazilian cohort and both 1000 KGP and ExAC. These differences were observed in several relevant genes including CYP3A4, NAT2 and SLCO1B1. Conclusion: We concluded that the Brazilian population needs clinical assessment of drug treatment based on individual genotype rather than ethnicity. (AU)

• Processo FAPESP: 15/16291-0 - Frequência de polimorfismos nos genes responsáveis pela absorção, distribuição, metabolismo e excreção (ADME) de medicamentos em pacientes portadores de carcinoma hepatocelular e hepatite C
• Beneficiário: Suzane Kioko Ono
• Linha de fomento: Auxílio à Pesquisa - Regular