The association between HLA-DQB1 polymorphism and antituberculosis drug-induced liver injury: a Case-Control Study

2014 ◽  
Vol 40 (1) ◽  
pp. 110-115 ◽  
Author(s):  
R. Chen ◽  
Y. Zhang ◽  
S. Tang ◽  
X. Lv ◽  
S. Wu ◽  
...  
2004 ◽  
Vol 58 (1) ◽  
pp. 71-80 ◽  
Author(s):  
Francisco J. de Abajo ◽  
Dolores Montero ◽  
Mariano Madurga ◽  
Luis A. Garcia Rodriguez

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shixian Chen ◽  
Hongqiu Pan ◽  
Yongzhong Chen ◽  
Lihuan Lu ◽  
Xiaomin He ◽  
...  

Abstract Reactive metabolites of anti-tuberculosis (anti-TB) drugs can result in excessive reactive oxygen species (ROS), which are responsible for drug-induced liver injury. The nuclear factor erythroid 2-related factor 2 (Nrf2) - antioxidant response elements (ARE) (Nrf2-ARE) signaling pathway plays a crucial role in protecting liver cells from ROS, inducing enzymes such as phase II metabolizing enzymes and antioxidant enzymes. Based on a Chinese anti-TB treatment cohort, a nested case-control study was performed to explore the association between 13 tag single-nucleotide polymorphisms (tagSNPs) in the NRF2, KEAP1, MAFF, MAFK genes in Nrf2-ARE signaling pathway and the risk of anti-TB drug-induced liver injury (ATLI) in 314 cases and 628 controls. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) after adjusting weight and usage of hepatoprotectant. Patients carrying the TC genotype at rs4243387 or haplotype C-C (rs2001350-rs6726395) in NRF2 were at an increased risk of ATLI (adjusted OR = 1.362, 95% CI: 1.017–1.824, P = 0.038; adjusted OR = 2.503, 95% CI: 1.273–4.921, P = 0.008, respectively), whereas patients carrying TC genotype at rs2267373 or haplotype C-G-C (rs2267373-rs4444637-rs4821767) in MAFF were at a reduced risk of ATLI (adjusted OR = 0.712, 95% CI: 0.532–0.953, P = 0.022; adjusted OR = 0.753, 95% CI: 0.587–0.965, P = 0.025, respectively). Subgroup analysis also detected a significant association between multiple tagSNPs (rs4821767 and rs4444637 in MAFF, rs4720833 in MAFK) and specific clinical patterns of liver injury under different genetic models. This study shows that genetic polymorphisms of NRF2, MAFF and MAFK may contribute to the susceptibility to ATLI in the Chinese anti-TB treatment population.


2004 ◽  
Vol 18 (2) ◽  
pp. 201-206 ◽  
Author(s):  
I. Lacroix ◽  
M. Lapeyre-Mestre ◽  
H. Bagheri ◽  
A. Pathak ◽  
J.L. Montastruc ◽  
...  

2016 ◽  
Vol 82 (1) ◽  
pp. 238-248 ◽  
Author(s):  
Monia Donati ◽  
Anita Conforti ◽  
Maria Carmela Lenti ◽  
Annalisa Capuano ◽  
Oscar Bortolami ◽  
...  

2018 ◽  
Vol 32 ◽  
pp. 205873841881628 ◽  
Author(s):  
Bilin Tao ◽  
Shixian Chen ◽  
Guancheng Lin ◽  
Miaomiao Yang ◽  
Lihuan Lu ◽  
...  

Uridine 5’-diphospho-glucuronosyl-transferase 1A1 (UGT1A1) plays an important role in the biliary excretion of bilirubin, suggesting genetic polymorphisms of UGT1A1 may have an impact on bile acid metabolism, which may be related to the development of anti-tuberculosis drug-induced liver injury (ATLI). This study explores the associations between genetic polymorphisms of UGT1A1 and ATLI in a Chinese anti-tuberculosis population. A 1:2 matched case–control study was conducted among 290 ATLI cases and 580 controls, of which causality assessment of ATLI cases was based on the updated Roussel Uclaf Causality Assessment Method (RUCAM). Conditional logistic regression was applied to calculate odds ratio (OR) and 95% confidence intervals (CIs), with weight and use of hepatoprotectant as covariates. The Bonferroni correction was used to adjust P values for multiple testing. Compared with those carrying rs6719561 TT genotype, patients with TC genotype had lower risk of ATLI (adjusted OR = 0.723, 95% CI: 0.531–0.985, P = 0.040). The haplotype TAG (rs3755319-rs2003569-rs4148323) could marginally significantly increase the risk of ATLI (adjusted OR = 5.071, 95% CI: 1.007–25.531, P = 0.049), while haplotype TC (rs4148329-rs6719561) could reduce the risk of ATLI (adjusted OR = 0.719, 95% CI: 0.527–0.982, P = 0.038). Patients with polymorphisms at rs4148328 or rs3755319 were at a reduced risk of moderate and severe liver injury under different genetic models. Based on this case–control study, genetic polymorphisms of UGT1A1 may be associated with susceptibility to ATLI in the Chinese anti-tuberculosis population.


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