Genetic and Epigenetic Basis of Drug-Induced Liver Injury

Snigdha Singh; P.V.S.N. Kiran Kumar; J. Pradeep Kumar; Sojit Tomo; Dharamveer Yadav; Praveen Sharma; Mahadev Rao; Mithu Banerjee

doi:10.1055/a-2097-0531

Seminars in Liver Disease, Inhaltsverzeichnis

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

Authors

Snigdha Singh

¹Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
P.V.S.N. Kiran Kumar

¹Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
J. Pradeep Kumar

¹Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
Sojit Tomo

¹Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
Dharamveer Yadav

¹Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
Praveen Sharma

¹Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
Mahadev Rao

²Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka, India
Mithu Banerjee

¹Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

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

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