Relationship of NAT2, CYP2E1 and GSTM1/GSTT1 polymorphisms with mild elevation of liver enzymes in Brazilian individuals under anti-tuberculosis drug therapy.
Clin Chim Acta
; 415: 215-9, 2013 Jan 16.
Article
em En
| MEDLINE
| ID: mdl-23099118
ABSTRACT
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 polymorphisms and concomitant use of CYP2E1 inhibitors contribute to the susceptibility to mild alterations in liver enzymes in patients under anti-tuberculosis drug therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Arilamina N-Acetiltransferase
/
Tuberculose Pulmonar
/
Inibidores Enzimáticos
/
Glutationa Transferase
/
Fígado
/
Antituberculosos
Limite:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
America do sul
/
Brasil
Idioma:
En
Revista:
Clin Chim Acta
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Brasil