Global pharmacogenomics: Impact of population diversity on the distribution of polymorphisms in the CYP2C cluster among Brazilians

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorSUAREZ-KURTZ, G.
dc.contributor.authorGENRO, J. P.
dc.contributor.authorMORAES, M. O. de
dc.contributor.authorOJOPI, E. B.
dc.contributor.authorPENA, S. D. J.
dc.contributor.authorPERINI, J. A.
dc.contributor.authorRIBEIRO-DOS-SANTOS, A.
dc.contributor.authorROMANO-SILVA, M. A.
dc.contributor.authorSANTANA, I.
dc.contributor.authorSTRUCHINER, C. J.
dc.date.accessioned2013-07-30T15:18:54Z
dc.date.available2013-07-30T15:18:54Z
dc.date.issued2012
dc.description.abstractThe impact of biogeographical ancestry, self-reported 'race/color' and geographical origin on the frequency distribution of 10 CYP2C functional polymorphisms (CYP2C8*2, *3, *4, CYP2C9*2, *3, *5, *11, CYP2C19*2, *3 and *17) and their haplotypes was assessed in a representative cohort of the Brazilian population (n = 1034). TaqMan assays were used for allele discrimination at each CYP2C locus investigated. Individual proportions of European, African and Amerindian biogeographical ancestry were estimated using a panel of insertion-deletion polymorphisms. Multinomial log-linear models were applied to infer the statistical association between the CYP2C alleles and haplotypes (response variables), and biogeographical ancestry, self-reported Color and geographical origin (explanatory variables). The results showed that CYP2C19*3, CYP2C9*5 and CYP2C9*11 were rare alleles (<1%), the frequency of other variants ranged from 3.4% (CYP2C8*4) to 17.3% (CYP2C19*17). Two distinct haplotype blocks were identified: block 1 consists of three single nucleotide polymorphisms (SNPs) (CYP2C19*17, CYP2C19*2 and CYP2C9*2) and block 2 of six SNPs (CYP2C9*11, CYP2C9*3, CYP2C9*5, CYP2C8*2, CYP2C8*4 and CYP2C8*3). Diplotype analysis generated 41 haplotypes, of which eight had frequencies greater than 1% and together accounted for 96.4% of the overall genetic diversity. The distribution of CYP2C8 and CYP2C9 (but not CYP2C19) alleles, and of CYP2C haplotypes was significantly associated with self-reported Color and with the individual proportions of European and African genetic ancestry, irrespective of Color self-identification. The individual odds of having alleles CYP2C8*2, CYP2C8*3, CYP2C9*2 and CYP2C9*3, and haplotypes including these alleles, varied continuously as the proportion of European ancestry increased. Collectively, these data strongly suggest that the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of pharmacogenomic studies of the CYP2C cluster in order to avoid spurious conclusions based on improper matching of study cohorts. This conclusion extends to other polymorphic pharmacogenes among Brazilians, and most likely to other admixed populations of the Americas. The Pharmacogenomics Journal (2012) 12, 267-276; doi: 10.1038/tpj.2010.89; published online 21 December 2010
dc.description.indexMEDLINE
dc.description.sponsorshipFinanciadora de Estudos e Projetos (FINEP) [01.08.01230.00]
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)
dc.identifier.citationPHARMACOGENOMICS JOURNAL, v.12, n.3, p.267-276, 2012
dc.identifier.doi10.1038/tpj.2010.89
dc.identifier.issn1470-269X
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/1079
dc.language.isoeng
dc.publisherNATURE PUBLISHING GROUP
dc.relation.ispartofPharmacogenomics Journal
dc.rightsrestrictedAccess
dc.rights.holderCopyright NATURE PUBLISHING GROUP
dc.subjectBrazilians
dc.subjectbiogeographical ancestry
dc.subjectCYP2C polymorphisms
dc.subjecthuman diversity
dc.subjectpopulation admixture
dc.subject.othermetabolism
dc.subject.otherportuguese
dc.subject.otherrelevant
dc.subject.wosGenetics & Heredity
dc.subject.wosPharmacology & Pharmacy
dc.titleGlobal pharmacogenomics: Impact of population diversity on the distribution of polymorphisms in the CYP2C cluster among Brazilians
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalSUAREZ-KURTZ, G.:Inst Nacl Canc INCA, Div Farmacol, Rio De Janeiro, Brazil
hcfmusp.author.externalGENRO, J. P.:Univ Fed Rio Grande do Sul, Dept Genet, Porto Alegre, RS, Brazil
hcfmusp.author.externalMORAES, M. O. de:Univ Fed Ceara, Dept Fisiol & Farmacol, Fac Med, Fortaleza, Ceara, Brazil
hcfmusp.author.externalPENA, S. D. J.:Univ Fed Minas Gerais, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil; GENE Nucleo Genet Med, Belo Horizonte, MG, Brazil
hcfmusp.author.externalPERINI, J. A.:Inst Nacl Canc INCA, Div Farmacol, Rio De Janeiro, Brazil
hcfmusp.author.externalRIBEIRO-DOS-SANTOS, A.:Fed Univ Para, Lab Genet Humana & Med, Guama, Brazil
hcfmusp.author.externalROMANO-SILVA, M. A.:Univ Fed Minas Gerais, Lab Neurociencia, Fac Med, Belo Horizonte, MG, Brazil
hcfmusp.author.externalSANTANA, I.:Inst Nacl Canc INCA, Div Farmacol, Rio De Janeiro, Brazil
hcfmusp.author.externalSTRUCHINER, C. J.:Fundacao Oswaldo Cruz, Programa Comp Cient, Rio De Janeiro, Brazil
hcfmusp.citation.scopus39
hcfmusp.contributor.author-fmusphcELIDA PAULA BENQUIQUE OJOPI
hcfmusp.description.beginpage267
hcfmusp.description.endpage276
hcfmusp.description.issue3
hcfmusp.description.volume2012
hcfmusp.origemWOS
hcfmusp.origem.pubmed21173785
hcfmusp.origem.scopus2-s2.0-84861458604
hcfmusp.origem.wosWOS:000304439200011
hcfmusp.publisher.cityLONDON
hcfmusp.publisher.countryENGLAND
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hcfmusp.remissive.sponsorshipCNPq
hcfmusp.remissive.sponsorshipFAPERJ
hcfmusp.remissive.sponsorshipFINEP
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