Manuscript Title:

ASSOCIATION OF GSTT1 AND GSTM1 POLYMORPHISM WITH ANTI TB DRUG INDUCED HEPATOTOXICITY

Author:

MUHAMMAD HAROON, AISHA SIDDIQUE, ADEELA SAUD, FAWAD ALI, MUHAMMAD ALI, KHAN NIAZ KHAN, UMAIR AKBAR

DOI Number:

DOI:10.17605/OSF.IO/52XVR

Published : 2022-12-10

About the author(s)

1. MUHAMMAD HAROON - Department of Biosciences, Park road, Chak-Shahzad, COMSATS University, Islamabad-Pakistan.
2. AISHA SIDDIQUE - Department of Microbiology, Women University, Mardan, Pakistan.
3. ADEELA SAUD - Department of Animal Sciences, Karakoram International University, Gilgit Pakistan.
4. FAWAD ALI - Institute of Biotechnology and Microbiology Bacha Khan University Charsadda Pakistan.
5. MUHAMMAD ALI - Institute of Biotechnology and Microbiology Bacha Khan University Charsadda Pakistan.
6. KHAN NIAZ KHAN - Department of Biology, Edwardes College Peshawar, Pakistan.
7. UMAIR AKBAR - Institute of Biotechnology and Microbiology Bacha Khan University Charsadda Pakistan.

Full Text : PDF

Abstract

Combined therapy is used for the treatment of tuberculosis, which includes Isoniazid, Pyrazinamide and Rifampicin. It has been reported that Glutathione-S- transferases play an important role in elimination of toxic reactive metabolites of anti-tuberculosis drugs produced via cytochrome’s metabolism. Inter individual variation to hepatotoxicity may be due to polymorphism in these genes. This candidate gene case-control study was carried out in 2019 to investigate the association of GSTT1 and GSTM1 polymorphism with hepatotoxicity. 243 patients were recruited for the study, in which 132 were cases and 111 were controls. Polymerase chain reaction based detection method was used to study polymorphism. The study indicated that GSTM1 and GSTT1 null genotypes may not be associated with hepatotoxicity (p=0.9, p=0.8). However, multi drug resistance is significantly associated with hepatotoxicity (p=0.0001, OR=7.9). Also, GSTT1 null genotype may be associated with multi drug resistance (p=0.01, OR=2.12). It is concluded that due to diminished activity of GSTs enzymes hepatotoxic intermediates are not further detoxified, causing hepatotoxicity. So it can be inferred that GSTT1 null genotype may be associated with hepatotoxicity in MDR TB patients.


Keywords

GST, GSTT1, GSTM1, Tuberculosis, Hepatotoxicity, Anti-TB Drugs, Anti-TB Drug Induced Hepatotoxicity.