Roles of NR1I3 and NR1H4 polymorphisms in the susceptibility to antituberculosis drug-induced liver injury in China: a case‒control study.

IF 2.8 3区生物学 Q2 GENETICS & HEREDITY Frontiers in Genetics Pub Date : 2024-10-23 eCollection Date: 2024-01-01 DOI:10.3389/fgene.2024.1428319

Xiaoyan Xu, Ruina Chen, Lihuan Lu, Jingru Cheng, Xiaomin He, Hongqiu Pan, Meiling Zhang, Honggang Yi, Shaowen Tang

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Abstract

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 sex. 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.

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NR1I3和NR1H4多态性在中国抗结核药物所致肝损伤易感性中的作用：一项病例对照研究。

目的：抗结核药物诱发肝损伤（AT-DILI）的发病机制在很大程度上仍不清楚。本研究旨在确定中国人群中核受体1亚家族I群成员3（NR1I3）和核受体1亚家族H群成员4（NR1H4）基因对AT-DILI风险的遗传贡献：进行了一项1:4匹配病例对照研究，检测并评估了NR1I3和NR1H4基因中的5个单核苷酸多态性（SNPs）。利用多变量条件逻辑回归模型，研究了单倍型和基因型对 AT-DILI 风险的影响。根据性别进行了扩展亚组分析。结果：本研究纳入了 224 例 AT-DILI 病例和 896 例对照。AT-DILI 病例和对照组的基因型或单倍型频率没有明显差异。然而，肝功能指标的比较显示，NR1H4 rs56163822 不同基因型患者的丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和总胆红素（TBil）的峰值存在显著差异（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. 30.0 U/L, p = 0.020）。31.0 U 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），以及不同 NR1H4 rs56163822 基因型男性患者的 ALT 和 AST 峰值（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）：基于这项1:4个体匹配病例对照研究，NR1H4基因中的SNP rs56163822可能与接受抗结核治疗的中国患者的AT-DILI易感性有关。要验证我们的研究结果，还需要在更多不同人群中开展进一步研究。

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来源期刊

Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

5.50

自引率

8.10%

发文量

3491

审稿时长

14 weeks

期刊介绍： Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.