Hepatic Injury and Glutathione s-transferase Deletion Related to Antituberculosis Use: An Observational Study in Balinese Population, Indonesia
BACKGROUND: Glutathione S-transferase (GST), together with other drug-metabolizing enzymes (N-acetyltransferase and cytochrome P450), plays a crucial role in the metabolism of isoniazid (isonicotinic acid hydrazide). Among five isoforms of GST, GSTM1, and GSTT1 had been proved to involve in isoniazid metabolism.
AIM: We aimed to investigate association between GST deletion and hepatic injury in the Indonesian population.
METHODS: This is a cross-sectional study. The total participants’ number was 70. Our whole blood samples were collected from adult pulmonary tuberculosis patients who received antituberculosis treatment category one in Bali. Detection for GSTM1 and GSTT1 deletion performed with the polymerase chain reaction technique using internal standard β-globin. Data analysis performed with the Chi-square test.
RESULTS: The proportion of GSTM1 null was 71.4% whereas the GSTT1 null was 34.3%. The proportion of combined GSTM1 null and GSTT1 null was 22.9%. There was no significant difference in liver damage incidence between GSTM1 null and wild-type (p > 0.005). There was also no significant difference in liver damage incidence between GSTT1 null and wild-type (p > 0.005).
CONCLUSIONS: Neither GSTM1 nor GSTT1 deletion proved to be associated with liver injury regarding antituberculosis use.
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Lv X, Tang S, Xia Y, Zhang Y, Wu S, Yang Z, et al. NAT2 genetic polymorphisms and antituberculosis drug-induced hepatotoxicity in Chinese community population. Ann Hepatol. 2012;11(5):700-7. https://doi.org/10.1016/ s1665-2681(19)31446-2 PMid:22947533
Bose PD, Sarma MP, Medhi S, Das BC, Husain SA, Kar P. Role of polymorphic N-acetyl transferase2 and cytochrome P4502E1 gene in antituberculosis treatment-induced hepatitis. J Gastroenterol Hepatol. 2011;26(2):312-8. https://doi. org/10.1111/j.1440-1746.2010.06355.x PMid:21261721
Arbex MA, Varella MC, deSiqueira HR, de Mello FA. Antituberculosis drugs: Drug interaction, adverse effects, and use in special situations. Part 1: First-line drugs. J Bras Pneumol. 2010;36(5):626-40. PMid:21085830
Stimimann G, Kessebohm K, Lauterburg B. Liver injury caused by drugs: An update. Swiss Med Wkly. 2010;140:w13080. https://doi.org/10.4414/smw.2010.13080 PMid:20927685
Chen M, Suzuki A, Borlak J, Andrade RJ, Isabel M, Lucena MI. Drug-induced liver injury: Interactions between drug properties and host factors. J Hepatol. 2015;63(2):503-14. https://doi. org/10.1016/j.jhep.2015.04.016 PMid:25912521
Huang Y. Recent progress in genetic variation and risk of antituberculosis drug-induced liver injury. J Chin Med Assoc. 2014;77(4):169-73. https://doi.org/10.1016/j.jcma.2014.01.010 PMid:24593909
Oh RC, dan Hustead TR. Causes and evaluation of mildly elevated liver transaminase levels. Am Fam Physician. 2011;84:1003-8.
Cai L, Cai M, Wang M, Xu Y, Chen W, Qin S, et al. Meta-analysis-based preliminary exploration of the connection between atdili and schizophrenia by GSTM1/T1 gene polymorphisms. PLoS One. 2015;10(6):e0128643. https://doi.org/10.1371/journal. pone.0128643 PMid:26046920
Wang T, Yu HT, Wang W, Pan YY, He LX, Wang ZY. Genetic polymorphisms of cytochrome p450 and glutathione s-transferase associated with antituberculosis drug-induced hepatotoxicity in Chinese tuberculosis patients. J Int Med Res. 2010;38(3):977- 986. https://doi.org/10.1177/147323001003800324 PMid:20819434
Teixeira RL, Morato RG, Cabello PH, Munizz LM, Moreira AS, Kritski AL, et al. Genetic polymorphisms of NAT2, CYP2E1 and GST enzymes and the occurrence of antituberculosis drug-induced hepatitis in Brazilian TB patients. Mem Inst Oswaldo Cruz. 2011;106(6):716-724. https://doi.org/10.1590/ s0074-02762011000600011 PMid:22012226
Santos EA, Goncalves JC, Fleury MK, Kritski AL, Oliveira MM, Velasque LS, et al. Relationship of anti-tuberculosis drug-induced liver injury and genetic polymorphisms in CYP2E1 and GST. Braz J Infect Dis. 2019;23(6):381-7. https://doi. org/10.1016/j.bjid.2019.09.003 PMid:31697922
Gupta VH, Singh M, Amarapurkar DN, Sasi P, Joshi JM, Baijal R, et al. Association of GST null genotypes with antituberculosis drug induced hepatotoxicity in Western Indian population. Ann Hepatol. 2013;12(6):959-65. https://doi.org/10.1016/ s1665-2681(19)31302-x PMid:24114827
Tang SW, Lv XZ, Zhang Y, Wu SS, Yang ZR, Xia YY, et al. CYP2E1, GSTM1andGSTT1 genetic polymorphisms and susceptibility to antituberculosis drug-induced hepatotoxicity: A nested case-control study. J Clin Pharm Ther. 2012;37(5):588-93. https://doi. org/10.1111/j.1365-2710.2012.01334.x PMid:22335459
Chatterjee S, Lyle N, Mandal A, Kundu S. GSTT1 and GSTM1 gene deletions are not associated with hepatotoxicity caused by antitubercular drugs. J Clin Pharm Ther. 2010;35(4):465-70. https://doi.org/10.1111/j.1365-2710.2009.01101.x PMid:20853551
Kim SH, Yoon HJ, Shin DH, Park SS, Kim YS, Park JS, et al. GSTT1 and GSTM1 null mutations and adverse reactions induced by antituberculosis drugs in Koreans. Tuberculosis (Edinb). 2010;90(1):39-43. https://doi.org/10.1016/j. tube.2009.12.001 PMid:20036620
Rana SV, Sharma SK, Ola RP, Kamboj JK, Malik A, Morya RK, et al. N-acetyltransferase 2, cytochrome p4502e1 and glutathione s-transferase genotypes in antitubercular treatment-induced hepatotoxicity in North Indians. J Clin Pharm Ther. 2014;39(1):91-6. https://doi.org/10.1111/jcpt.12105 PMid:24188272
Forestiero FJ, Cecon L, Hirata MH, de Melo FF, Cardoso RF, Cerda A, et al. 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. 2013;415:215-9. https://doi.org/10.1016/j. cca.2012.10.030 PMid:23099118
Cai Y, Yi JY, Zhou CH, Shen XZ. Pharmacogenetic study of drug-metabolizing enzyme polymorphism on the risk of antituberculosis drug-induced liver injury: A meta-analysis. PLoS One. 2012;7(10):e47769. https://doi.org/10.1371/journal. pone.0047769 PMid:23082213
Li C, Long J, Hu X, Zhou Y. GSTM1 and GSTT1 genetic polymorphisms and risk of anti-tuberculosis drug-induced hepatotoxicity: An updated meta-analysis. Eur J Clin Microbiol Infect Dis. 2013;32(7):859-68. https://doi.org/10.1007/ s10096-013-1831-y PMid:23377313
Yang S, Hwang SJ, Park JY, Chung EK, Lee JI. Association of genetic polymorphisms of CYP2E1, NAT2, GST and SLCO1B1 with the risk of antituberculosis drug-induced liver injury: A systematic review and meta-analysis. BMJ Open. 2019;9(8):e027940. https://doi.org/10.1136/bmjopen-2018-027940 PMid:31375612
Feng FM, Guo M, Chen Y, Li SM, Zhang P, Sun SF, et al. Genetic polymorphisms in metabolic enzymes and susceptibility to anti-tuberculosis drug-induced hepatic injury. Genet Mol Res. 2014;13(4):9463-71. https://doi.org/10.4238/2014. november.11.11 PMid:25501156
Xiang Y, Ma L, Wu W, Liu W, Li Y, Zhu X, et al. The incidence of liver injury in uyghur patients treated for tb in xinjiang uyghur autonomous region, China, and its association with hepatic enzyme polymorphisms NAT2, CYP2E1, GSTM1 and GSTT1. PloS One. 2014;9(1):e85905. https://doi.org/10.1371/journal. pone.0085905 PMid:24465778
Liu F, Jiao A, Wu X, Zhao W, Yin Q, Qi H, et al. Impact of glutathione s-transferase M1 and T1 on anti-tuberculosis drug-induced hepatotoxicity in Chinese pediatric patients. PLoS One. 2014;9(12):e115410. https://doi.org/10.1371/journal. pone.0115410 PMid:25525805
Singla N, Gupta D, Birbian N, Singh J. Association of NAT2, GST and CYP2E1 polymorphisms and anti-tuberculosis drug-induced hepatotoxicity. Tuberculosis (Edinb). 2014;94(3):293-8. https://doi.org/10.1016/j.tube.2014.02.003 PMid:24637014
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