Frequency of genetic polymorphisms of PXR gene in the Brazilian population

Autor(es)

Moreira, Ricardo P. P. ^[1] ; Jorge, Alexander A. L. ^[2] ; Mendonca, Berenice B. ^[1] ; Bachega, Tania A. S. S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Disciplina Endocrinol, Unidade Endocrinol Desenvolvimento, Lab Hormonios, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Disciplina Endocrinol, Unidade Endocrinol Genet LIM 25, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinics; v. 66, n. 6, p. 1041-1044, 2011.
• Citações Web of Science: 6

Resumo

INTRODUCTION: PXR polymorphisms have been implicated in modulating CYP3A4 and PXR expression, potentially accounting for interindividual differences in drug metabolism. The prevalence of PXR polymorphisms varies among ethnic groups and data on the allelic distribution in the highly mixed Brazilian population is lacking. The aim of this study was to analyze genetic variations in the PXR gene in Brazilians and to compare the results to other ethnic groups. METHODS: DNA samples from 117 healthy Brazilians underwent PCR amplification and sequencing. RESULTS: Eleven polymorphisms were identified, 3 of which are highly associated with differences in CYP3A4 expression. We also identified 1 new synonymous variant in 1.3% of the alleles. Among the functional polymorphisms, -25913C>T and -6994T>C occurred at a higher frequency compared to the African alleles (p<0.05) but at a lower frequency compared to Caucasian alleles. The 8055C>T allele was found at a similar frequency to those described in Caucasians and Africans (p>0.05). CONCLUSION: We observed that functional variants of the PXR were frequent in our sample of the Brazilian population. Our results suggest that PXR gene variants may be of interest in pharmacogenetic studies involving Brazilians. (AU)

• Processo FAPESP: 08/50959-4 - Análise de fatores genéticos moduladores da resposta à terapia com acetado de cortisona em pacientes com a forma clássica da deficiência da 21-hidroxilase
• Beneficiário: Ricardo Paranhos Pires de Moreira
• Linha de fomento: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 09/54394-4 - Análise dos fatores genéticos envolvidos no desenvolvimento da síndrome metabólica durante a terapia com glicocorticóide em pacientes portadores da deficiência da 21-hidroxilase
• Beneficiário: Ricardo Paranhos Pires de Moreira
• Linha de fomento: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 05/04726-0 - Caracterização molecular das doenças endócrinas congênitas que afetam o crescimento e o desenvolvimento
• Beneficiário: Ana Claudia Latronico Xavier
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/54238-2 - Análise do efeito modulatório de polimorfismos nos genes CYP3A7, POR e NR3C1 na terapia com glicocorticóide da forma clássica da deficiência da 21-hidroxilase
• Beneficiário: Tania Aparecida Sartori Sanchez Bachega
• Linha de fomento: Auxílio à Pesquisa - Regular