Genetic Variants of GBP4: Reduced Risks for Drug-Induced Acute Liver Failure in Non-Finnish European Population

IF 6 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Liver International Pub Date : 2025-01-27 DOI:10.1111/liv.70011

Tsung-Jen Liao, Menghang Xia, Paul Hayashi, Bohun Pan, Guruprasad P. Aithal, M. Isabel Lucena, Raúl J. Andrade, Jody A. Rule, William M. Lee, Jorge Rakela, Ruili Huang, Minjun Chen

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Abstract

Background and Aims

Acute liver failure (ALF) is a serious condition, typically in individuals without prior liver disease. Drug-induced ALF (DIALF) constitutes a major portion of ALF cases. Our research aimed to identify potential genetic predispositions to DIALF.

Methods

We analysed the potential genetic variants associated with DIALF using the whole exome sequencing data from 75 cases, including 40 non-Finnish European cases in the pilot study. Chi-square tests were performed for case–control analysis against the 1000 genomes project as the control. A replication study of 44 DIALF cases that included 24 non-Finnish Europeans was conducted to validate candidate variants. The association between clinical phenotype and genotypes was analysed using one-way analysis of variance.

Results

Eight variants (rs561037, rs561042, rs608339, rs655260, rs1142886, rs1142888, rs1142889 and rs1142890) in the guanylate binding protein 4 (GBP4) were significantly associated with DIALF in non-Finnish Europeans in the pilot study and confirmed in the replication study. Rs561037 and rs561042 were highly significant with the lowest allele frequencies in both pilot and replication studies. An association was also found between these variants and milder clinical outcomes, indicated by lower peak levels of ALT, AST and higher Karnofsky performance scores.

Conclusion

Our study identified eight GBP4 missense variants linked to a lower risk of DIALF in the non-Finnish European population. The GBP4 protein, activated by interferon-gamma, plays a critical role in innate immunity. These findings suggest that GBP4 variants might influence immune and inflammatory responses in DIALF, though further studies are needed to elucidate the underlying mechanisms.

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来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.