Pregnane-X-Receptor Genotype and Hepatotoxic Incidence on Tuberculosis Patients Receiving Antituberculosis in Bali
Abstract
Background: Drug-induced liver injury might lead to serious illness. One of the drugs that potentially toxic to the liver is antituberculosis. Many factors could influence antituberculosis-induced liver injury, including genetic variation. One of such genetic variation is polymorphism of pregnane-x-receptor (PXR) gene. PXR plays a crucial role in the regulation of many drug metabolizing enzymes and drug transporters. The association between PXR polymorphism and hepatotoxic incidence in several studies showed the inconsistent result. Therefore, it’s very important to study the PXR genotype pattern and its relation with hepatotoxic incidence among tuberculosis patients who received antituberculosis treatment. This study aimed to investigate the incidence of hepatotoxic according to PXR genotype pattern among tuberculosis patients who received antituberculosis treatment in Bali. Methods: This study was a cross-sectional study. About 65 subjects were enrolled in this study, selected from tuberculosis patients who attended the pulmonary outpatient clinic of Sanglah Hospital, Bali Indonesia and received the antituberculosis drug. Identification of PXR genotype was performed using PCR/RFLP technique with MboI restriction enzyme. Results: The proportion of wild type and mutant genotype of PXR were 72.3% and 27.7%, respectively. There was no significant difference in the proportion of hepatotoxic between wild type and mutant genotype of PXR. Conclusion: There was no significant difference in the proportion of hepatotoxic between wild type and mutant genotype of PXR on tuberculosis patients who received antituberculosis in Bali.
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REFERENCES
1. Devarbhavi H (2012) An update on drug-induced liver injury. Journal of Clinical and Experimental Hepatology, 2(3):247-259.
Lee WM (2003) Drug-induced hepatotoxicity. New England Journal of Medicine, 349:474-485.
Navarro VJ, Senior JR (2006) Drug-related hepatotoxicity. New England Journal of Medicine, 354:731-739.
Arbex MA, Varella MCL, deSiqueira HR, deMello FAF (2010) Antituberculosis drugs: drug interaction, adverse effects and use in special situations. Journal of Brasil Pneumology, 36(5):626-640.
Teixeira RLF, Morato RG, Cabello PH, Muniz LMK, Moreira ASR, Kritski AL, et al (2011) Genetic polymorphisms of NAT2, CYP2E1 and GST enzymes and the occurrence of antituberculosis drug-induced hepatitis in Brazilian TB patients. Mem Inst Oswaldo Cruz, 106(6):716-724.
Lv X, Tang S, Xia Y, Zhang Y, Wu S, Yang Z, et al (2012) NAT2 genetic polymorphisms and antituberculosis drug-induced hepatotoxicity in Chinese community population. Annals of Hepatology, 11(5):700-707.
Huang YS, Chern HD, Su WJ, Wu JC, Lai SL, Yang SY, et al (2002) Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug–induced hepatitis. Hepatology, 35:883-889.
Lee SW, Chung LSC, Huang HH, Chuang TY, Liou YH, Wu LSH (2010) NAT2 and CYP2E1 polymorphisms and susceptibility to first line antituberculosis drug-induced hepatitis. International Journal of Tuberculosis and Lung Disease, 14(5):622-626.
Bose PD, Sarma MP, Medhi S, Kar PDas BC, Husain SA, (2011) Role of polymorphic N-acetyl transferase2 and cytochrome P4502E1 gene in antituberculosis treatment-induced hepatitis. Journal of Gastroenterology and Hepatology, 26(2):312–318.
Shehu AI, Li C, Xie W, Ma X (2016) The pregnane x receptor in tuberculosis therapeutics. Expert Opinion on Drug Metabolism and Toxicology, 12(1):21-30.
Zazuli Z, Barliana MI, Mulyani UA, Perwitasari DA, Ng H, Absulah R (2015) Polymorphism of pxr gene associated with the increased risk of drug-induced liver injury in Indonesian pulmonary tuberculosis patients. Journal of Clinical Pharmaceutical Therapy, 40(6):690-684.
Wang JY, Tsai CH, Lee YL, Lee LN, Hsu CL, Chang HC, et al (2015) Gender-dimorphic impact of pxr genotype and haplotype on hepatotoxicity during antituberculosis treatment. Medicine, 94(24):e982.
Wang Y, Chai SC, Brewer CT, Chen T (2014) Pregnane x receptor and drug-induced liver injury. Expert Opinion On Drug Metabolism and Toxicology, 10(11):1521-1532.
Scheer N, Ross J, Rode A, Zevnik B, Niehaves S, Faust N, et al (2008) A novel panel of mouse models to evaluate the role of human pregnane x receptor and constitutive androstane receptor in drug response. The Journal of Clinical Investigation, 118(9):3228-3239.
Pavek P (2016) Pregnane x receptor-mediated gene repression and cross talk of pxr with other nuclear receptors via coactivator interactions. Frontiers in Pharmacology, 7(456):1-16.
Wang Y, Ong SS, Chai SC, Chen T (2012) Role of car and pxr in xenobiotic sensing and metabolism. Expert Opinion on Drug Metabolism and Toxicology, 8(7):803-817.
Yan J and Xie W (2016) A brief history of the discovery of pxr and car as xenobiotic receptors. Acta Pharmaceutica Sinica B, 6(5):450-452.
Zhang L, Qiu F, Lu X, Li Y, Fang W, Zhang L, et al (2014) A functional polymorphism in the 3’utr of pxr interacts with smoking to increase lung cancer risk in southern and eastern chinese smoker. International Journal of Molecular Science, 15:17457-17468.
Brewer CT dan Chen T (2016) PXR variants: the impact on drug metabolism and therapeutic responses. Acta Pharmaceutia B, 6(5):441-449.
Lim Y and Huang J (2008) Interplay of pregnane x receptor with other nuclear receptors on gene regulation. Drug Metabolism and Pharmacokinetics, 23(1):14-21.
Konno Y, Neoishi M, Kodama S (2008) The role of nuclear receptors car and pxr in hepatic energy metabolism. Drug Metabolism and Pharmacokinetics, 23(1):8-13.
Qiu Z, Cervantes JL, Cicek BB, Mukherjee S, Venkatesh M, Maher LA, et al (2016) Pregnane x receptor regulates patogen-induced inflammation and host defense against an intracellular bacterial infection through toll-like receptor 4. Scientific Reports, 6:31936.
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