Global pharmacogenomics: distribution of CYP3A5 polymorphisms and phenotypes in the Brazilian population.

The influence of self-reported "race/color", geographical origin and genetic ancestry on the distribution of three functional CYP3A5 polymorphisms, their imputed haplotypes and inferred phenotypes was examined in 909 healthy, adult Brazilians, self-identified as White, Brown or Black (&quo...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Guilherme Suarez-Kurtz, Daniela D Vargens, Ana Beatriz Santoro, Mara H Hutz, Maria Elisabete de Moraes, Sérgio D J Pena, Ândrea Ribeiro-dos-Santos, Marco A Romano-Silva, Claudio José Struchiner
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2477138d92774fe38c50b8d69ae2e214
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2477138d92774fe38c50b8d69ae2e214
record_format	dspace
spelling	oai:doaj.org-article:2477138d92774fe38c50b8d69ae2e2142021-11-18T08:38:04ZGlobal pharmacogenomics: distribution of CYP3A5 polymorphisms and phenotypes in the Brazilian population.1932-620310.1371/journal.pone.0083472https://doaj.org/article/2477138d92774fe38c50b8d69ae2e2142014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24427273/?tool=EBIhttps://doaj.org/toc/1932-6203The influence of self-reported "race/color", geographical origin and genetic ancestry on the distribution of three functional CYP3A5 polymorphisms, their imputed haplotypes and inferred phenotypes was examined in 909 healthy, adult Brazilians, self-identified as White, Brown or Black ("race/color" categories of the Brazilian census). The cohort was genotyped for CYP3A53 (rs776746), CYP3A56 (rs10264272) and CYP3A57 (rs41303343), CYP3A5 haplotypes were imputed and CYP3A5 metabolizer phenotypes were inferred according to the number of defective CYP3A5 alleles. Estimates of the individual proportions of Amerindian, African and European ancestry were available for the entire cohort. Multinomial log-linear regression models were applied to infer the statistical association between the distribution of CYP3A5 alleles, haplotypes and phenotypes (response variables), and self-reported Color, geographical region and ancestry (explanatory variables). We found that Color per se or in combination with geographical region associates significantly with the distribution of CYP3A5 variant alleles and CYP3A5 metabolizer phenotypes, whereas geographical region per se influences the frequency distribution of CYP3A5 variant alleles. The odds of having the default CYP3A53 allele and the poor metabolizer phenotype increases continuously with the increase of European ancestry and decrease of African ancestry. The opposite trend is observed in relation to CYP3A56, CYP3A57, the default CYP3A5*1 allele, and both the extensive and intermediate phenotypes. No significant effect of Amerindian ancestry on the distribution of CYP3A5 alleles or phenotypes was observed. In conclusion, this study strongly supports the notion that the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of pharmacogenomic studies, and dealt with as a continuous variable, rather than proportioned in arbitrary categories that do not capture the diversity of the population. The relevance of this work extrapolates the Brazilian borders, and extends to other admixed peoples of the Americas, with ancestral roots in Europe, Africa and the American continent.Guilherme Suarez-KurtzDaniela D VargensAna Beatriz SantoroMara H HutzMaria Elisabete de MoraesSérgio D J PenaÂndrea Ribeiro-dos-SantosMarco A Romano-SilvaClaudio José StruchinerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e83472 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guilherme Suarez-Kurtz Daniela D Vargens Ana Beatriz Santoro Mara H Hutz Maria Elisabete de Moraes Sérgio D J Pena Ândrea Ribeiro-dos-Santos Marco A Romano-Silva Claudio José Struchiner Global pharmacogenomics: distribution of CYP3A5 polymorphisms and phenotypes in the Brazilian population.
description	The influence of self-reported "race/color", geographical origin and genetic ancestry on the distribution of three functional CYP3A5 polymorphisms, their imputed haplotypes and inferred phenotypes was examined in 909 healthy, adult Brazilians, self-identified as White, Brown or Black ("race/color" categories of the Brazilian census). The cohort was genotyped for CYP3A53 (rs776746), CYP3A56 (rs10264272) and CYP3A57 (rs41303343), CYP3A5 haplotypes were imputed and CYP3A5 metabolizer phenotypes were inferred according to the number of defective CYP3A5 alleles. Estimates of the individual proportions of Amerindian, African and European ancestry were available for the entire cohort. Multinomial log-linear regression models were applied to infer the statistical association between the distribution of CYP3A5 alleles, haplotypes and phenotypes (response variables), and self-reported Color, geographical region and ancestry (explanatory variables). We found that Color per se or in combination with geographical region associates significantly with the distribution of CYP3A5 variant alleles and CYP3A5 metabolizer phenotypes, whereas geographical region per se influences the frequency distribution of CYP3A5 variant alleles. The odds of having the default CYP3A53 allele and the poor metabolizer phenotype increases continuously with the increase of European ancestry and decrease of African ancestry. The opposite trend is observed in relation to CYP3A56, CYP3A57, the default CYP3A5*1 allele, and both the extensive and intermediate phenotypes. No significant effect of Amerindian ancestry on the distribution of CYP3A5 alleles or phenotypes was observed. In conclusion, this study strongly supports the notion that the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of pharmacogenomic studies, and dealt with as a continuous variable, rather than proportioned in arbitrary categories that do not capture the diversity of the population. The relevance of this work extrapolates the Brazilian borders, and extends to other admixed peoples of the Americas, with ancestral roots in Europe, Africa and the American continent.
format	article
author	Guilherme Suarez-Kurtz Daniela D Vargens Ana Beatriz Santoro Mara H Hutz Maria Elisabete de Moraes Sérgio D J Pena Ândrea Ribeiro-dos-Santos Marco A Romano-Silva Claudio José Struchiner
author_facet	Guilherme Suarez-Kurtz Daniela D Vargens Ana Beatriz Santoro Mara H Hutz Maria Elisabete de Moraes Sérgio D J Pena Ândrea Ribeiro-dos-Santos Marco A Romano-Silva Claudio José Struchiner
author_sort	Guilherme Suarez-Kurtz
title	Global pharmacogenomics: distribution of CYP3A5 polymorphisms and phenotypes in the Brazilian population.
title_short	Global pharmacogenomics: distribution of CYP3A5 polymorphisms and phenotypes in the Brazilian population.
title_full	Global pharmacogenomics: distribution of CYP3A5 polymorphisms and phenotypes in the Brazilian population.
title_fullStr	Global pharmacogenomics: distribution of CYP3A5 polymorphisms and phenotypes in the Brazilian population.
title_full_unstemmed	Global pharmacogenomics: distribution of CYP3A5 polymorphisms and phenotypes in the Brazilian population.
title_sort	global pharmacogenomics: distribution of cyp3a5 polymorphisms and phenotypes in the brazilian population.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/2477138d92774fe38c50b8d69ae2e214
work_keys_str_mv	AT guilhermesuarezkurtz globalpharmacogenomicsdistributionofcyp3a5polymorphismsandphenotypesinthebrazilianpopulation AT danieladvargens globalpharmacogenomicsdistributionofcyp3a5polymorphismsandphenotypesinthebrazilianpopulation AT anabeatrizsantoro globalpharmacogenomicsdistributionofcyp3a5polymorphismsandphenotypesinthebrazilianpopulation AT marahhutz globalpharmacogenomicsdistributionofcyp3a5polymorphismsandphenotypesinthebrazilianpopulation AT mariaelisabetedemoraes globalpharmacogenomicsdistributionofcyp3a5polymorphismsandphenotypesinthebrazilianpopulation AT sergiodjpena globalpharmacogenomicsdistributionofcyp3a5polymorphismsandphenotypesinthebrazilianpopulation AT andrearibeirodossantos globalpharmacogenomicsdistributionofcyp3a5polymorphismsandphenotypesinthebrazilianpopulation AT marcoaromanosilva globalpharmacogenomicsdistributionofcyp3a5polymorphismsandphenotypesinthebrazilianpopulation AT claudiojosestruchiner globalpharmacogenomicsdistributionofcyp3a5polymorphismsandphenotypesinthebrazilianpopulation
_version_	1718421487834103808

Global pharmacogenomics: distribution of CYP3A5 polymorphisms and phenotypes in the Brazilian population.

Ejemplares similares