• GITA WIDI SETYOWATI Department of Biological Pharmacy, Biotechnology Pharmacy Laboratory, Faculty of Pharmacy, UniversitasPadjadjaran, Bandung, Indonesia
  • NURUL ANNISA Department of Biological Pharmacy, Biotechnology Pharmacy Laboratory, Faculty of Pharmacy, UniversitasPadjadjaran, Bandung, Indonesia, Unit of Clinical Pharmacy and Community, Faculty of Pharmacy, UniversitasMulawarman, Samarinda, Indonesia
  • MELISA I. BARLIANA Department of Biological Pharmacy, Biotechnology Pharmacy Laboratory, Faculty of Pharmacy, UniversitasPadjadjaran, Bandung, Indonesia, Center of Excellence in Higher Education for Pharmaceutical Care Innovation, UniversitasPadjadjaran, Bandung, Indonesia



Antituberculosisdrugs, Genetic polymorphism, Tuberculosis


Tuberculosis (TB) has been identified as one of the most highly infectious diseases in the world. Tuberculosis can be identified as pulmonary or extrapulmonary. Therapy for TB is a combination of several drugs in one treatment. The effectiveness and toxicity of TB therapy may differ in each patient because of some risk factors, especially genetic variations. This review describes several genes that can affect the effectiveness and toxicity of antituberculosis drugs, namely UGT1A1, SLCO1B1, NAT2, and CYP2E1. This review was conducted utilizing the PubMed database, with keywords used as follows: polymorphism, antituberculosis, and tuberculosis. The presence of polymorphisms in these genes can result in hepatotoxicity and decreased drug bioavailability. Therefore, polymorphisms in these genes can determine the effectiveness of TB therapy.


Download data is not yet available.


Houben RMGJ, Dodd PJ. The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling. PLoS Med 2016;13:1–13.

Uplekar M, Weil D, Lonnroth K, Jaramillo E, Lienhardt C, Dias HM, et al. WHO’s new end TB strategy. Lancet 2015;385:1799–801.

WHO. Moscow declaration ending tb in the sustainable development era; 2017. p. 1–8.

Sun Q, Zhang Q, Gu J, Sun WW, Wang P, Bai C, et al. Prevalence, risk factors, management, and treatment outcomes of first-line antituberculous drug-induced liver injury: a prospective cohort study. Pharmacoepidemiol Drug Saf 2016;25:908–17.

Setiawan SI, Ascobat P. Adverse reactions to first-line anti-tuberculosis drugs as a risk factor of pulmonary tuberculosis treatment default in Jakarta, Indonesia. Int J Appl Pharm 2019;11(Special Issue 6):80–3.

Siddiqui S, Baig MMA, Jaffer S, Ansari SFR. Study on prevalence of adverse drug reactions in patients suffering from tuberculosis in a tertiary care hospital. Int J Pharm Pharm Sci 2016;8:375–7.

Buntoro IF, Kristin E, Sumardi. Decrease of liver function after treatment of antituberculosis drugs in tuberculosis patients with malnutrition and alcohol consumption. Int J Pharm Pharm Sci 2016;8:269–73.

Urban TJ, Goldstein DB, Watkins PB. Genetic basis of susceptibility to drug-induced liver injury: what have we learned and where do we go from here? Pharmacogenomics 2012;13:735–8.

Gumbo T, Louie A, Deziel MR, Parsons LM, Salfinger M, Drusano GL.Selection of a moxifloxacin dose that suppresses drug resistance in mycobacterium tuberculosis, by use of an in vitro pharmacodynamic infection model and mathematical modeling. J Infect Dis 2004;190:1642–51.

Kruglyak L, Nickerson DA. Variation is the spice of life. Nat Genet 2001;27:234–6.

Balram C, Sabapathy K, Fei G, Khoo KS, Lee EJD. Genetic polymorphisms of UDP-glucuronosyltransferase in Asians: UGT1A1* 28 is a common allele in Indians. Pharmacogenet Genomics 2002;12:81-3.

Guillemette C, Millikan RC, Newman B, Housman DE. Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 and association with breast cancer among African Americans. Cancer Res 2000;60:950–6.

Zhang A, Xing Q, Qin S, Du J, Wang L, Yu L, et al. Intra-ethnic differences in genetic variants of the UGT-glucuronosyltransferase 1A1 gene in Chinese populations. Pharmacogenomics J 2007;7:333–8.

Pacheco PR, Brilhante MJ, Ballart C, Sigalat F, Polena H, Cabral R, et al. UGT1A1, UGT1A6, and UGT1A7 genetic analysis. Mol Diagn Ther 2009;13:261–8.

Pasanen MK, Neuvonen M, Neuvonen PJ, Niemi M. SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid. Pharmacogenet Genomics 2006;16:873–9.

Pasanen MK, Fredrikson H, Neuvonen PJ, Niemi M. Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. Clin Pharmacol Ther 2007;82:726–33.

NCBI. NAT2 N-acetyltransferase 2; 2020. Available from: [Last accessed on 20 Jul 2020]

NCBI. CYP2E1 cytochrome P450 family 2 subfamily E member 1; 2020. Available from: [Last accessed on 20 Jul 2020]

Chang JC, Liu EH, Lee CN, Lin YC, Yu MC, Bai KJ, et al. UGT1A1 polymorphisms associated with risk of induced liver disorders by anti-tuberculosis medications. Int J Tuberc Lung Dis 2012;16:376–8.

Sun Q, Liu H, Zheng R, Wang P, Liu Z, Sha W, et al. Genetic polymorphisms of SLCO1B1, CYP2E1 and UGT1A1 and susceptibility to anti-tuberculosis drug-induced hepatotoxicity: a chinese population-based prospective case-control study. Clin Drug Investig 2017;37:1125–36.

Chen R, Wang J, Tang SW, Zhang Y, Lv XZ, Wu SS, et al. CYP7A1, BAAT and UGT1A1 polymorphisms and susceptibility to anti-tuberculosis drug-induced hepatotoxicity. Int J Tuberc Lung Dis 2016;20:812–8.

Chen R, Wang J, Tang S, Zhang Y, Lv X, Wu S, et al. Association of polymorphisms in drug transporter genes (SLCO1B1 and SLC10A1) and anti-tuberculosis drug-induced hepatotoxicity in a Chinese cohort. Tuberculosis 2015;95:68–74.

Kim SH, Kim SH, Lee JH, Lee BH, Kim YS, Park JS, et al. Polymorphisms in drug transporter genes (ABCB1, SLCO1B1, and ABCC2) and hepatitis induced by antituberculosis drugs. Tuberculosis 2012;92:100–4.

Sloan DJ, McCallum AD, Schipani A, Egan D, Mwandumba HC, Ward SA, et al. Genetic determinants of the pharmacokinetic variability of rifampin in Malawian adults with pulmonary tuberculosis. Antimicrob Agents Chemother 2017;61:1–9.

Dompreh A, Tang X, Zhou J, Yang H, Topletz A, Ahwireng A, et al. Effect of genetic variation of NAT2 on isoniazid and SLCO1B1 and CES2 on rifampin pharmacokinetics in ghanaian children with tuberculosis. Antimicrob Agents Chemother 2018;62:1–11.

An HR, Wu XQ, Wang ZY, Zhang JX, Liang Y. NAT2 and CYP2E1 polymorphisms associated with antituberculosis drug-induced hepatotoxicity in Chinese patients. Clin Exp Pharmacol Physiol 2012;39:535–43.

Yuliwulandari R, Susilowati RW, Wicaksono BD, Viyati K, Prayuni K, Razari I, et al. NAT2 variants are associated with the drug-induced liver injury caused by anti-tuberculosis drugs in Indonesian patients with tuberculosis. J Hum Genet 2016;61:533–7.

Singla N, Gupta D, Birbian N, Singh J. Association of NAT2, GST and CYP2E1 polymorphisms and anti-tuberculosis drug-induced hepatotoxicity. Tuberculosis 2014;94:293–8.

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;9:1–8.

Ben Mahmoud L, Ghozzi H, Kamoun A, Hakim A, Hachicha H, Hammami S, et al. Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatotoxicity in Tunisian patients with tuberculosis. Pathol Biol 2012;60:324–30.

Verhagen LM, Coenen MJ, López D, García JF, De Waard JH, Schijvenaars MM, et al. Full-gene sequencing analysis of NAT2 and its relationship with isoniazid pharmacokinetics in venezuelan children with tuberculosis. Pharmacogenomics 2014;15:285–96.

Kim SH, Kim SH, Yoon HJ, Shin DH, Park SS, Kim YS, et al. NAT2, CYP2C9, CYP2C19, and CYP2E1 genetic polymorphisms in anti-TB drug-induced maculopapular eruption. Eur J Clin Pharmacol 2011;67:121–7.

Tang SW, Lv XZ, Zhang Y, Wu SS, Yang ZR, Xia YY, et al. CYP2E1, GSTM1, and GSTT1 genetic polymorphisms and susceptibility to antituberculosis drug-induced hepatotoxicity: a nested case-control study. J Clin Pharm Ther 2012;37:588–93.

Tang S, Lv X, Zhang Y, Wu S, Yang Z, Xia Y, et al. Cytochrome P450 2E1 gene polymorphisms/haplotypes and anti-tuberculosis drug-induced hepatitis in a chinese cohort. PLoS One 2013;8:1–7.

Sharma SK, Jha BK, Sharma A, Sreenivas V, Upadhyay V, Jaisinghani C, et al. Genetic polymorphisms of CYP2E1 and GSTM1 loci and susceptibility to anti-tuberculosis drug-induced hepatotoxicity. Int J Tuberc Lung Dis 2014;18:588–93.

Charbonneau DH, Healy AM. Genetics home reference. J Consum Health Internet 2005;9:61–8.

Genetics Home Reference. UGT1A1 gene; 2020. Available from: [Last accessed on 20 Jul 2020]

Hennig S, Naiker S, Reddy T, Egan D, Kellerman T, Wiesner L, et al. Effect of SLCO1B1 polymorphisms on rifabutin pharmacokinetics in African HIV-infected patients with tuberculosis. Antimicrob Agents Chemother 2015;60:617–20.

Weiner M, Peloquin C, Burman W, Luo CC, Engle M, Prihoda TJ, et al. Effects of tuberculosis, race, and human gene SLCO1B1 polymorphisms on rifampin concentrations. Antimicrob Agents Chemother 2010;54:4192–200.

Bins S, Lenting A, El Bouazzaoui S, van Dorn L, Oomen-de Hoop E, Eskens FALM, et al. Polymorphisms in SLCO1B1 and UGT1A1 are associated with sorafenib-induced toxicity. Pharmacogenomics 2016;17:1483–90.

Genetics Home Reference. SLCO1B1 gene; 2020. Available from: [Last accessed on 20 Jul 2020].

SNPedia. NAT2; 2020. Available from: [Last accessed on 20 Jul 2020].

Genetics Home Reference. NAT2 gene; 2020. Available from: [Last accessed on 20 Jul 2020].

Teixeira RL de F, Renata Gomes Morato PHC, Muniz LMK, Moreira A da SR, Afrânio Lineu Kritski FCQM, Suffys PN, 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;106:716–24.

Lee SW, Chung LSC, Huang HH, Chuang TY, Liou YH, Wu LSH. NAT2 and CYP2E1 polymorphisms and susceptibility to first-line anti-tuberculosis drug-induced hepatitis. Int J Tuberc Lung Dis 2010;14:622–6.

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;38:977–86.

Huang YS, Chern H Der, Su WJ, Wu JC, Chang SC, Chiang CH, et al. Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis. Hepatology 2003;37:924–30.

Ahlawat S, Sharma R, Maitra A, Roy M, Tantia MS. Designing, optimization, and validation of tetra-primer ARMS PCR protocol for genotyping mutations in caprine Fec genes. Meta Gene 2014;2:439–49.



How to Cite

SETYOWATI, G. W., ANNISA, N., & BARLIANA, M. I. (2021). CORRELATION OF GENETIC POLYMORPHISM IN UGT1A1, SLCO1B1, NAT2, AND CYP2E1 WITH HEPATOTOXICITY. International Journal of Applied Pharmaceutics, 13(1), 53–58.



Review Article(s)