Relationships of GCLM, GCLC and GSTP1 gene polymorphisms in patients with anti-tuberculosis drug-induced liver injury

Abstract

Abstract: Objective To analyze the relationship of polymorphisms of glutamate cysteine ligase modifier (GCLM) subunit, glutamate cysteine ligase catalytic (GCLC) subunit and glutathione S transferase P1 (GSTP1) with acute anti-tuberculosis drug-induced liver injury (AADILI).Methods In our study, 92 cases with AADILI were enrolled as the study group and 86 cases without AADILI were enrolled as the control group. T-588C loci of GCLM gene, C-129T loci of GCLC gene and Ile105Val loci of GSTP1 gene were detected using polymerase chain reaction restriction fragment length polymorphism. Representativeness of genotype frequencies were verified using Hardy-Weinberg equilibrium. Factors related to the occurrence of AADILI were analyzed using Logistic method.Results There were single nucleotide polymorphisms (SNPs) at T-588C loci of GCLM gene, C-129T loci of GCLC gene and Ile105Val loci of GSTP1 gene, which were stable and in accordance with Hardy-Weinberg equilibrium. There were significant differences in genotype distributions of TT at GCLM T-588C loci, CC at GCLC C-129T loci and GG at GSTP1 Ile105Val loci between the 2 groups (P< 0.05). Genotypes of TT at GCLM T-588C loci, CC at GCLC C-129T loci and GG at GSTP1 Ile105Val loci were risk factors for AADILI.Conclusion The SNPs of GCLM T-588C, GCLC C-129T and GSTP1 Ile105Val genes are associated with AADILI susceptibility. TT at GCLM T-588C loci, CC at GCLC C-129T loci and GG at GSTP1 Ile105Val loci can increase the risk of AADILI.

Key words: Glutamate cysteine ligase, Glutathione S transferase P1, Acute anti-tuberculosis drug-induced liver injury

WANG Yun, BAO Jing. Relationships of GCLM, GCLC and GSTP1 gene polymorphisms in patients with anti-tuberculosis drug-induced liver injury[J]. Chinese Hepatolgy, 2019, 24(2): 138-142.

References

[1] 温祝社,胡国信,郑洁,等. 药物性肝损伤168例临床分析. 广西医学,2016,38:574-576.
[2] Chalasani NP,Hayashi PH,Bonkovsky HL,et al. ACG Clinical Guideline:the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol,2014,109:950-966.
[3] Skvortsova L,Perfelyeva A,Khussainova E,et al. Association of GCLM -588C/T and GCLC -129T/C promoter polymorphisms of genes coding the subunits of glutamate cysteine ligase with ischemic heart disease development in kazakhstan population. Dis Markers,2017,2017: 4209257.
[4] Yuniastuti A,Susanti R,Mustikaningtyas D. Polymorphism of glutamate-cysteine ligase subunit catalytic (GCLC) gene in pulmonary tuberculosis patients. Park J Biol Sci,2017,20:397-402.
[5] Sharma N,Singh A,Singh N,et al. Genetic polymorphisms in GSTM1,GSTT1 and GSTP1 genes and risk of lung cancer in a North Indian population. Cancer Epidemiol,2015,39:947-955.
[6] 中华医学会结核病学分会. 肺结核病诊断和治疗指南. 中华结核和呼吸杂志,2001,24:70-74.
[7] 中华医学会结核病学分会,《中华结核和呼吸杂志》编辑委员会. 抗结核药所致药物性肝损伤诊断与处理专家建议. 中华结核和呼吸杂志,2013,10:732-736.
[8] 程璘令,刘雅雅,刘君,等. 谷氨酰半胱氨酸连接酶催化亚单位基因甲基化而非多态性与慢性阻塞性肺疾病相关. 中华生物医学工程杂志,2014,20:185-190.
[9] Saini N,Bakshi S,Sharma S. In-silico approach for drug induced liver injury prediction: Recent advances. Toxicol Lett,2018,295:288-295.
[10] 赖清谊. 抗结核药物对肺结核患者肝功能影响因素分析. 中国现代药物应用,2015,9:172-174.
[11] Mizrahi M,Adar T,Lalazar G,et al. Glycosphingolipids prevent APAP and HMG-CoA reductase inhibitors-mediated liver damage:a novel method for “safer drug” formulation that prevents drug-induced liver injury. J Clin Transl Hepatol,2018,6:127-134.
[12] Prers PS,Valerio A,Cadena SM,et al. Glutathione modifies the oxidation products of 2′-deoxyguanosine by singlet molecular oxygen. Arch Biochem Biophys,2015,586:33-34.
[13] 王换换,申正杰,肖航,等. 热应激对肝脏中Keapl—Nrf2信号通路及下游基因表达的影响. 南京农业大学学报,2017,40:151-156.
[14] Park JW,Choi JY,Hong SA,et al. Exercise induced upregulation of glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modifier subunit gene expression in Thoroughbred horses. Asian-Australas J Anim Sci,2017,30:728-735.
[15] Brown RH,Reynolds C,Brooker A,et al. Sulforaphane improves the bronchoprotective response in asthmatics through Nrf2-mediated gene pathways. Respir Res,2015,16:1-12.
[16] Ari Y,Irawan Y,Muh N,et al. Association of -129C/T promoter GCLC polymorphism with glutathione plasma level in pulmonary tuberculosis patients. Arpn J of Engineering and Applied Sciences,2017,9:3006-3010.
[17] 曾丽平,吴和平,伍世挥,等. 谷胱甘肽硫转移酶M1基因缺失与结直肠癌预后的关系. 广西医学,2016,38:932-934.
[18] Yuan ZJ,Zhou WW,Liu W,et al. Association of GSTP1 and RRM1 polymorphisms with the response and toxicity of gemcitabine-cisplatin combination chemotherapy in chinese patients with non-small cell lung cancer. Asian Pac J Cancer Prev,2015,16:4347-4351.
[19] Zhang Y,Yuan Y,Chen Y,et al. Association between GSTP1 Ile105Val polymorphism and urinary system cancer risk:evidence from 51 studies. Onco Targets Ther,2016,9:3565-3569.
[20] 李曙波,廖长秀,罗莹,等. 人工修饰双等位基因特异性引物结合SYBR Green Ⅰ荧光PCR法检测GSTP1基因多态性. 广东医学,2017,38:1998-2001.