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ORIGINAL RESEARCH article

Front. Genet.
Sec. Pharmacogenetics and Pharmacogenomics
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1428319

Roles of NR1I3 and NR1H4 polymorphisms in the susceptibility to antituberculosis druginduced liver injury in China: A case-control study

Provisionally accepted
Xiaoyan Xu Xiaoyan Xu 1Ruina Chen Ruina Chen 2Lihuan Lu Lihuan Lu 3Jingru Cheng Jingru Cheng 2Xiaomin He Xiaomin He 4Hongqiu Pan Hongqiu Pan 5Meiling Zhang Meiling Zhang 6Honggang Yi Honggang Yi 2Shaowen Tang Shaowen Tang 2*
  • 1 Changshu Center for Disease Control and Prevention, Suzhou, China
  • 2 Nanjing Medical University, Nanjing, China
  • 3 The Second People’s Hospital of Changshu, Changshu, China
  • 4 The People’s Hospital of Taixing, Taixing, China
  • 5 The Third People’s Hospital of Zhenjiang Affiliated to Jiangsu University, Zhenjiang, China
  • 6 The Jurong Hospital Affiliated to Jiangsu University, Jurong, China

The final, formatted version of the article will be published soon.

    Objective: The pathogenesis of antituberculosis drug-induced liver injury (AT-DILI) remains largely unknown. The current investigation aimed to determine the genetic contribution of the nuclear receptor subfamily 1 Group I member 3 (NR1I3) and nuclear receptor subfamily 1 Group H member 4 (NR1H4) genes to the risk of AT-DILI in the Chinese population.Methods: A 1:4 matched case-control study was conducted, and five single nucleotide polymorphisms (SNPs) in the NR1I3 and NR1H4 genes were detected and assessed. Utilizing a multivariate conditional logistic regression model, the effects of haplotype and genotype on the risk of AT-DILI were examined. Extended subgroup analysis was carried out based on patient sex and hospital. The distribution of the peak value of serum liver enzymes also compared among different genotypes.Results: 224 AT-DILI cases and 896 controls were included in this study. No significant difference was observed in genotypes or haplotypes frequencies between AT-DILI cases and controls. However, comparisons of liver function indicators revealed significant differences in the peak values of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) among patients with different genotypes of NR1H4 rs56163822 (GG vs. GT vs. TT, 27.1 U/L vs. 26.0 U/L vs. 23.0 U/L, p = 0.020; 34.0 U/L vs. 31.0 U/L vs. 30.6 U/L, p = 0.008; 15.5 μmol/L vs. 15.0 μmol/L vs. 13.7 μmol/L, p = 0.029, respectively), as well as in the peak values of ALT and AST among male patients with different genotypes of NR1H4 rs56163822 (29.0 U/L vs. 26.9 U/L vs. 22.6 U/L, p = 0.002; 34.0 U/L vs. 32.0 U/L vs. 30.5 U/L, p = 0.019, respectively).Conclusion: Based on this 1:4 individual-matched case-control study, the SNP rs56163822 in the NR1H4 gene may be linked to the susceptibility to AT-DILI in Chinese patients receiving anti-TB treatment. Further studies in larger varied populations are needed to validate our findings.

    Keywords: antituberculosis drug-induced liver injury, Nuclear receptor subfamily 1 Group I member 3, Nuclear Receptor Subfamily 1 Group H Member 4, Genetic polymorphisms, Casecontrol study

    Received: 06 May 2024; Accepted: 08 Oct 2024.

    Copyright: © 2024 Xu, Chen, Lu, Cheng, He, Pan, Zhang, Yi and Tang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Shaowen Tang, Nanjing Medical University, Nanjing, China

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