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tagSNP rs1495741 as a useful molecular marker to predict antituberculosis drug-induced hepatotoxicity.
Chamorro, Julián G; Castagnino, Jorge P; Musella, Rosa M; Nogueras, Mabel; Frías, Ana; Visca, Mabel; Aidar, Omar; Costa, Lucas; de Larrañaga, Gabriela F.
Afiliação
  • Chamorro JG; aHemostasis and Thrombosis Laboratory bPneumotisiology Division cIntensive Care Department of Critical Infected Patient (D.A.I.P.I.C.), Hospital of Infectious Diseases 'F. J. Muñiz' dLaboratory for Biological and Artificial Learning, Instituto de Ciencias Básicas y Medicina Experimental, Hospital Italiano de Buenos Aires, Buenos Aires City, Argentina.
Pharmacogenet Genomics ; 26(7): 357-61, 2016 07.
Article em En | MEDLINE | ID: mdl-27104815
INTRODUCTION: It has been widely reported that the slow acetylator phenotype of N-acetyltransferase 2 (NAT2) is associated with the development of antituberculosis drug-induced hepatotoxicity (ATDH). The aim of this report was to evaluate the level of agreement and accuracy of two recently recommended markers, the two-single nucleotide polymorphisms (SNP) (C282T and T341C) and tagSNP of NAT2 (rs1495741) genotypes, to predict the seven-SNP-inferred NAT2 phenotype in Bolivian and Argentinian tuberculosis (TB)-patient populations. In addition, we analyzed the association of these markers with ATDH. METHODS: We examined 331 TB patients who had been treated with anti-TB drugs. TagSNP of NAT2 genotyping was determined using PCR-restriction fragment length polymorphisms. The seven SNPs of NAT2 were determined using sequencing. Concordance analysis was carried out using Kendall's tau-b coefficient (w) and the degree of agreement with Cohen's κ coefficient (κ). Receiver operating characteristic receiver operating characteristic curves were obtained to measure the specificity and sensitivity of the method. A binary logistic regression was performed to identify variables associated with the development of ATDH. RESULTS: Both predictors showed a remarkable concordance (>95.0%) and an almost perfect agreement (κ>0.945; P<0.0001) with the predicted acetylator profile. However, the sensitivity of the tagSNP genotypes to predict the NAT2 acetylator phenotype was lower in the Bolivian population (92.3%) compared with the Argentinian population (100.0%). CONCLUSION: A nearly perfect agreement between both predictors and the predicted acetylation profile was observed with very high levels of sensitivity (>97%) and specificity (>98.0%). Furthermore, and as expected, both the two-SNP (C282T, T341C) and tagSNP were found to be independent variables in predicting ATDH with the same strength as seven-SNP of NAT2.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Arilamina N-Acetiltransferase / Tuberculose / Polimorfismo de Nucleotídeo Único / Doença Hepática Induzida por Substâncias e Drogas / Antituberculosos Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Pharmacogenet Genomics Assunto da revista: FARMACOLOGIA / GENETICA MEDICA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Arilamina N-Acetiltransferase / Tuberculose / Polimorfismo de Nucleotídeo Único / Doença Hepática Induzida por Substâncias e Drogas / Antituberculosos Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Pharmacogenet Genomics Assunto da revista: FARMACOLOGIA / GENETICA MEDICA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos