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The roles of GSTM1 and GSTT1 null genotypes and other predictors in anti‐tuberculosis drug‐induced liver injury
Author(s) -
Monteiro T. P.,
ElJaick K. B.,
JeovanioSilva A. L.,
Brasil P. E. A. A.,
Costa M. J. M.,
Rolla V. C.,
de Castro L.
Publication year - 2012
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/j.1365-2710.2012.01368.x
Subject(s) - liver injury , genotype , medicine , tuberculosis , incidence (geometry) , drug , gastroenterology , immunology , pharmacology , pathology , biology , gene , genetics , physics , optics
Summary What is known and Objective: Anti‐tuberculosis drugs (ATD), although highly effective, often cause liver injury. Glutathione S‐transferases (GST) play a crucial protective role in the detoxifying mechanisms of drugs. Several studies have investigated the genetic null variants of GSTM1 and GSTT1 as possible risk factors for ATD‐induced liver injury; however, those findings are inconsistent. We investigated GSTM1 and GSTT1 null genotypes in Brazilian patients with tuberculosis (TB), adjusting for other possible predictors of ATD‐induced liver injury. Methods: This was a prospective cohort study with patients who were treated for TB from 2006 to 2011. GSTM1 and GSTT1 gene deletions were analysed from genomic DNA by polymerase chain reaction (PCR). Demographic, clinical and laboratory data were extracted from medical records and possible predictors of liver injury were evaluated. Results and Discussion: This study enrolled 177 patients. Anti‐tuberculosis drugs‐induced liver injury incidence was 33·3%. Hepatitis B infection (HBV) and increased alanine aminotransferase (ALT) baseline were significant predictors. Neither GSTM1 nor GSTT1 null genotypes were associated with ATD‐induced liver injury; nevertheless, the comparison among four different liver toxicity grades showed that GSTM1 non‐null genotype was significant more frequent among the higher grades of liver toxicity. What is new and Conclusion: GSTM1 and GSTT1 null genotypes do not seem to play important roles in ATD‐induced liver injury in Brazilians. However, there was evidence that GSTM1 polymorphisms were possibly related to the intensity of toxicity. Active HBV and initial high ALT could predict ATD‐induced liver injury.