Relationship between CYP2E1 Gene Polymorphism and Anti-tuberculosis Drug-induced Liver Injury

Source:
By:Donglin Zhu, Yun Xi, Jieming Dong, Fanhua Huang, Changzhi Xu, Gang Xiao

DOI: https://doi.org/10.30564/jams.v1i4.289

Abstract:

 Objective: To investigate the relationship between cytochrome P450 E1 (CYP2E1) gene polymorphisms and susceptibility to anti-tuberculosis drug-induced liver damage (ATDLI) in tuberculosis patients in the Chinese Han nationality. Methods: A retrospective analysis was performed on 360 patients with tuberculosis who had liver damage after tuberculosis treatment (case group) and 360 patients with tuberculosis who did not develop liver injury after treatment (control group). MassARRAY were used to detect CYP2E1 gene polymorphisms. Results: In a total of 8 tagged SNP loci selected, the rs8192773 locus failed to pass the test, and therefore, it is not included in subsequent analysis. At the remaining seven SNP sites, the difference in alleles was not statistically significant between the case group and the control group, suggesting that these sites may not be related to liver damage caused by anti-tuberculosis drugs. Three monomer domains were found in the seven tags SNP loci mentioned above. However, it was found that these haplotypes are not closely related to anti-tuberculosis drug-induced liver damage. Conclusion: The CYP2E1 gene polymorphism in the Chinese Han nationality is not related to the occurrence of anti-tuberculosis drug-induced liver injury.

References:

[1] Huang YS, Chern HD, Su WJ, et al. Cytochrome P450 2E1 genotype and the susceptibility to anti-tuberculosis drug-induced hepatitis[J]. Hepatology, 2003, 37(6):924-930. [2] Gupta VH, Amarapurkar DN, Singh M, et al. Association of N-acetyltransferase 2 and cytochrome P450 2E1 gene polymorphisms with antituberculosis drug-induced hepatotoxicity in Western India[J]. J Gastroenterol Hepatol, 2013, 28(8):1368-1374. [3] Jiang O, Zhou R, Wu D, et al. CYP2E1 polymorphisms and colorectal cancer risk: a HuGE systematic review and meta-analysis[J]. Tumour Biol, 2013, 34(2):1215-1224. [4] Munaka M, Kohshi K, Kawamoto T, et a1. Genetic polymorphism of tobacco and alcohol-related metabolizing enzymes and risk of hepatocellular carcinoma[J]. J Cancer Res Clin Oncol, 2003, 129(6): 355-360. [5] He X., Feng S. Role of metabolic enzymes P450 (CYP) on activating procarcinogen and their polymorphisms on the risk of cancers[J]. Current Drug Metabolism, 2015, 16(10):850-863. [6] N Ben Fredj, R Gam, E Kerkni, et al. Risk factors of isoniazid-induced hepatotoxicity in Tunisian tuberculosis patients[J]. The Pharmacogenomics Journal, 2017, 17(4): 372-377. [7] Dyah Aryani Perwitasari, Jarir Atthobari, Bob Wilffert. Pharmacogenetics of isoniazid-induced hepatotoxicity[J]. Drug Metabolism Reviews, 2015, 47(2): 222-228. [8] Roy B, Ghosh SK, Sutradhar D, et al. Predisposition of antituberculosis drug induced hepatotoxicity by cytochrome P450 2E1 genotype and haplotype in pediatric patients[J]. J Gastroenterol Hepatol. 2006, 21(4):784-786. [9] Chamorro JG, Castagnino JP, Aidar O, et al. Effect of gene-gene and gene-environment interactions associated with antituberculosis drug-induced hepatotoxicity[J].Pharmacogenet Genomics, 2017, 27(10):363-371. [10] Bose PD, Sarma MP, Medhi S, et al. Role ofpolymorphic N-acetyl transferase2 and cytochrome P4502E1 gene in antituberculosis treatment-induced hepatitis[J]. J Gastroenterol Hepatol, 2011, 26(2):312-318. [11] Yi-Shin Huang, Herng-Der Chern, Wei-Juin Su, et al. Polymorphism of the N-Acetyltransferase 2 Gene as a Susceptibility Risk Factor for Antituberculosis Drug–Induced Hepatitis[J]. Hepatology, 2002, 35(4):883-889. [12] Nicolas Vuilleumier, Michel F, Rossier, Alberto Chiappe, et al. CYP2E1 genotype and isoniazid- induced hepatotoxicity in patients treated for latent tuberculosis[J]. Eur J Clin Pharmacol, 2006, 62(6): 423-429. [13] T Wang, HT Yu, W Wang, et al. Genetic Polymorphisms of Cytochrome P450 and Glutathione S-transferase Associated with Antituberculosis Drug-induced Hepatotoxicity in Chinese Tuberculosis Patients[J]. J Int Med Res, 2010, 38(3):977-986. [14] Soukaina G, Ilham R, Fatima ZL et al. Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1 variants in Moroccan population[J]. BMC Genet, 2014, 15:156. [15] Teixeira RL, Morato RG, Cabello PH, et al. Genetic polymorphisms of NAT2, CYP2E1 and GST enzymes and the occurrence of antituberculosis drug-induced hepatitis in Brazilian TB patients[J]. Mem Inst Oswaldo Cruz, 2011, 106(6):716-724.