Unique CYP3A4 genetic variant in Brazilian tuberculosis patients with/without HIV

dc.creatorJeovanio-Silva, André L.
dc.creatorMonteiro, Thaís P.
dc.creatorEl-Jaick, Kênia B.
dc.creatorBrasil, Pedro E.A.A. do
dc.creatorRolla, Valéria C.
dc.creatorCastro, Liane
dc.date2019-10-22T12:35:43Z
dc.date2019-10-22T12:35:43Z
dc.date2012
dc.date.accessioned2023-09-26T20:40:04Z
dc.date.available2023-09-26T20:40:04Z
dc.identifierJEOVANIO-SILVA, André L. et al. Unique CYP3A4 genetic variant in Brazilian tuberculosis patients with/without HIV. Molecular Medicine Reports, v. 5, p. 153-161, 2012.
dc.identifier1791-2997
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/36622
dc.identifier10.3892/mmr.2011.602
dc.identifier1791-3004
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8861638
dc.descriptionCYP3A4 is involved in tuberculosis (TB) and human immunodeficiency virus (HIV) drug metabolism. Transcriptional activation by rifampicin involves the CYP3A4 gene 5'-upstream region. Consequently, variation may interfere with transcription and enzymatic activity and even drug response. However, genetic polymorphisms and distribution of CYP3A4 allelic frequencies in individuals from Rio de Janeiro remain unknown. The aim of this study was to conduct research into sequencing the CYP3A4 5'-upstream region in Brazilian patients with and without HIV. This follow-up study involved 106 individuals undergoing treatment for TB and/or HIV. The CYP3A4 5'-upstream region was analyzed using PCR, sequencing and clinical data. Male patients revealed a higher HIV frequency (p=0.021). The TB forms observed were pulmonary (48.1%), extrapulmonary (22.64%) and disseminated (27.36%). Lymph node form was the most frequent (70.83%) extrapulmonary form of TB. The only single nucleotide polymorphism detected in the population was c.-392A>G. Genotypes observed were CYP3A4*1A/CYP3A4*1A (45.3%), CYP3A4*1A/CYP3A4*1B (40.6%) and CYP3A4*1B/CYP3A4*1B (14.2%), revealing a different distribution with extrapulmonary TB cases (17.6% CYP3A4*1A/CYP3A4*1B and 23.5% CYP3A4*1B/CYP3A4*1B). The CYP3A4*1A allele was found to be associated with tobacco use. The CYP3A4*1B mutant allele occurred in 34% of patients. This study revealed that the CYP3A4 5'-upstream regulatory region was highly conserved with the exception of the -392 position. Genotype association with tobacco suggests that CYP3A4 may participate in tobacco metabolism. Genotype distribution inversion in extrapulmonary TB cases suggests that CYP3A4 may be involved in TB prognosis.
dc.description2020-04-22
dc.formatapplication/pdf
dc.languageeng
dc.publisherSpandidos Publications
dc.rightsopen access
dc.subjectBrazil
dc.subjectCYP3A4 promoter region
dc.subjectCYP3A4 upstream region sequence analysis
dc.subjectCYP3A4*1B
dc.subjectGenetic polymorphism
dc.subjectTuberculosis
dc.titleUnique CYP3A4 genetic variant in Brazilian tuberculosis patients with/without HIV
dc.typeArticle


Este ítem pertenece a la siguiente institución