Relationship of NAT2, CYP2E1 and GSTM1/GSTT1 polymorphisms with mild elevation of liver enzymes in Brazilian individuals under anti-tuberculosis drug therapy

Autor(es)

Forestiero, Francisco Jose ^[1] ; Cecon, Leticia ^[1] ; Hirata, Mario Hirouki ^[1] ; de Melo, Fernando Fiuza ^[2] ; Cardoso, Rosilene Fressatti ^[3] ; Cerda, Alvaro ^[1] ; Crespo Hirata, Rosario Dominguez ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Clin & Toxicol Anal, Sch Pharmaceut Sci, BR-05508000 Sao Paulo - Brazil

^[2] Clemente Ferreira Inst, Sao Paulo - Brazil

^[3] Univ Estadual Maringa, Dept Clin Anal & Biomed, Maringa, PR - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinica Chimica Acta; v. 415, p. 215-219, JAN 16 2013.
• Citações Web of Science: 8

Resumo

The relationship of NAT2, CYP2E1 and GSTM1/GSTT1 polymorphisms with mild elevation of liver biomarkers was investigated in individuals under anti-tuberculosis drug therapy. Tuberculosis outpatients (18-70 y) with (n = 59) and without (n = 40) mild increase of liver enzymes (MILE) at two-month treatment were selected. Blood samples were obtained for DNA extraction and evaluation of serum markers of liver function. NAT2, CYP2E1 and GSTM1/GSTT1 polymorphisms were detected by DNA sequencing, PCR-RFLP, and PCR multiplex. Frequency of NAT2{*}5/{*}5 genotype was higher in MILE than in non-MILE group (p = 0.04). Patients carrying NAT2{*}5/{*}5 genotype had increased susceptibility to MILE (OR: 9.00, 95CI: 1.46-55.48, p = 0.018). CYP2E1{*}5B allele ({*}1A/{*}5B plus {*}5B/{*}5B genotypes) carriers had a trend for reduced risk for MILE (OR: 0.34, 95CI: 0.11-1.03, p = 0.056) that was confirmed by lower levels of liver markers than CYP2E1{*}1A/{*}1A carriers after treatment (p < 0.05). Moreover, increased post-treatment ALT, AST and total bilirubin were associated with GSTM1{*}1/GSTT1{*}1 genotypes (p < 0.05). Patients taking CYP2E1 inhibitors had increased susceptibility to MILE (OR: 7.39, 95CI: 1.93-28.29, p = 0.003), which was independent of the studied polymorphisms. These results are suggestive that NAT2, CYP2E1 and GSTM1/GSTT1 polyrnorphisms and concomitant use of CYP2E1 inhibitors contribute to the susceptibility to mild alterations in liver enzymes in patients under anti-tuberculosis drug therapy. (c) 2012 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 04/08406-7 - Variantes genéticas da N-acetiltransferase: relação com a respsota terapêutica à isoniazida em pacientes com tuberculose
• Beneficiário: Rosario Dominguez Crespo Hirata
• Modalidade de apoio: Auxílio à Pesquisa - Regular