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

Vera Kim; Thijs Van Der Wal; Miriam Yumie Nishi; Luciana Ribeiro Montenegro; Flair Jose Carrilho; Yujin Hoshida; Suzane Kioko Ono

doi:10.2217/pgs-2020-0013

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

Vera Kim, Thijs Van Der Wal, Miriam Yumie Nishi, Luciana Ribeiro Montenegro, Flair Jose Carrilho, Yujin Hoshida, Suzane Kioko Ono

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	575-586
Number of pages	12
Journal	Pharmacogenomics
Volume	21
Issue number	9
DOIs	https://doi.org/10.2217/pgs-2020-0013
State	Published - Jun 2020
Externally published	Yes

Keywords

ADME genes
Brazilian
admixture population
genetic diversity
next-generation sequencing
pharmacogenomics

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmacology

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10.2217/pgs-2020-0013

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title = "Brazilian cohort and genes encoding for drug-metabolizing enzymes and drug transporters",

abstract = "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.",

keywords = "ADME genes, Brazilian, admixture population, genetic diversity, next-generation sequencing, pharmacogenomics",

author = "Vera Kim and Wal, {Thijs Van Der} and Nishi, {Miriam Yumie} and Montenegro, {Luciana Ribeiro} and Carrilho, {Flair Jose} and Yujin Hoshida and Ono, {Suzane Kioko}",

note = "Funding Information: V Kim would like to thank Coordenac¸{\~a}o de Aperfeic¸oamento de Pessoal de N{\'i}vel Superior (CAPES – 1399290) and Pro-grama de Doutorado Sandu{\'i}che no Exterior (PDSE 88881.132608/2016-01). SK Ono would like to thank Fundac¸{\~a}o de Amparo {\`a} pesquisa de S{\~a}o Paulo (FAPESP 2015/16291-0) and Brazilian Council for Development of Science and Technology (CNPq) for grant PQ 308609/2018-2. Y Hoshida would like to thank the US NIH/NIDDK R01 DK099558, European Commission ERCE2014EAdGE671231, Department of Defense W81XWHE16E1E0363 and the Cancer Prevention and Research Institute of Texas (CPRIT) RR180016. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Publisher Copyright: {\textcopyright} 2020",

year = "2020",

month = jun,

doi = "10.2217/pgs-2020-0013",

language = "English (US)",

volume = "21",

pages = "575--586",

journal = "Pharmacogenomics",

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T1 - Brazilian cohort and genes encoding for drug-metabolizing enzymes and drug transporters

AU - Kim, Vera

AU - Wal, Thijs Van Der

AU - Nishi, Miriam Yumie

AU - Montenegro, Luciana Ribeiro

AU - Carrilho, Flair Jose

AU - Hoshida, Yujin

AU - Ono, Suzane Kioko

N1 - Funding Information: V Kim would like to thank Coordenac¸ão de Aperfeic¸oamento de Pessoal de Nível Superior (CAPES – 1399290) and Pro-grama de Doutorado Sanduíche no Exterior (PDSE 88881.132608/2016-01). SK Ono would like to thank Fundac¸ão de Amparo à pesquisa de São Paulo (FAPESP 2015/16291-0) and Brazilian Council for Development of Science and Technology (CNPq) for grant PQ 308609/2018-2. Y Hoshida would like to thank the US NIH/NIDDK R01 DK099558, European Commission ERCE2014EAdGE671231, Department of Defense W81XWHE16E1E0363 and the Cancer Prevention and Research Institute of Texas (CPRIT) RR180016. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Publisher Copyright: © 2020

PY - 2020/6

Y1 - 2020/6

N2 - 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.

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KW - genetic diversity

KW - next-generation sequencing

KW - pharmacogenomics

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JO - Pharmacogenomics

JF - Pharmacogenomics

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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