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Semin Liver Dis 2023; 43(02): 163-175
DOI: 10.1055/a-2097-0531
Review Article

Genetic and Epigenetic Basis of Drug-Induced Liver Injury

Snigdha Singh
1   Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
,
P.V.S.N. Kiran Kumar
1   Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
,
J. Pradeep Kumar
1   Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
,
Sojit Tomo
1   Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
,
Dharamveer Yadav
1   Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
,
Praveen Sharma
1   Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
,
Mahadev Rao
2   Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka, India
,
Mithu Banerjee
1   Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
› Author Affiliations Funding Ad hoc project grant from the Indian Council of Medical Research under grant no. 5/8/5/45/multicentric study/2019/ECD-I.
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Abstract

Drug-induced liver injury (DILI) is a rare but severe adverse drug reaction seen in pharmacotherapy and a major cause of postmarketing drug withdrawals. Advances in genome-wide studies indicate that genetic and epigenetic diversity can lead to inter-individual differences in drug response and toxicity. It is necessary to identify how the genetic variations, in the presence of environmental factors, can contribute to development and progression of DILI. Studies on microRNA, histone modification, DNA methylation, and single nucleotide polymorphisms related to DILI were retrieved from databases and were analyzed for the current research and updated to develop this narrative review. We have compiled some of the major genetic, epigenetic, and pharmacogenetic factors leading to DILI. Many validated genetic risk factors of DILI, such as variants of drug-metabolizing enzymes, HLA alleles, and some transporters were identified. In conclusion, these studies provide useful information in risk alleles identification and on implementation of personalized medicine.

Keywords

drug-induced liver injury (DILI) - miRNA - DNA methylation - histone modifications - single nucleotide polymorphisms


Publication History

Accepted Manuscript online:
24 May 2023

Article published online:
05 July 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

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