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 G. STM1* 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. © 2012 Elsevier B.V.