PMID- 24879978
OWN - NLM
STAT- MEDLINE
DCOM- 20150223
LR  - 20220419
IS  - 1098-8971 (Electronic)
IS  - 0272-8087 (Linking)
VI  - 34
IP  - 2
DP  - 2014 May
TI  - Genetic basis of drug-induced liver injury: present and future.
PG  - 123-33
LID - 10.1055/s-0034-1375954 [doi]
AB  - There is considerable evidence that susceptibility to idiosyncratic drug-induced 
      liver injury (DILI) is genetically determined. Though genetic associations with 
      DILI have been reported since the 1980s, the development of genome-wide 
      association studies has enabled genetic risk factors for DILI, in common with 
      other diseases, to be detected and confirmed more confidently. Human leukocyte 
      antigen (HLA) genotype has been demonstrated to be a strong risk factor for 
      development of DILI with a range of drugs and the underlying mechanism, probably 
      involving presentation of a drug-peptide complex to T cells is increasingly well 
      understood. However, specific HLA alleles are not associated with all forms of 
      DILI and non-HLA genetic risk factors, especially those relating to drug 
      disposition, also appear to contribute. For some drugs, there is evidence of a 
      dual role for HLA and drug metabolism genes. Though the associations with non-HLA 
      genes have been less well replicated than the HLA associations, there is 
      increasing evidence that drug metabolism genes such as NAT2 and UGT2B7 contribute 
      to some forms of DILI. Translating current genetic findings on DILI 
      susceptibility to the clinic has been relatively slow, but some progress is now 
      being made. In the future, DNA sequencing may lead to the identification of rare 
      variants that contribute to DILI. Developments in the related area of epigenomics 
      and in the development of improved models for DILI by use of genetically defined 
      induced pluripotent stem cells should improve understanding of the biology of 
      DILI and inform drug development.
CI  - Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
FAU - Urban, Thomas J
AU  - Urban TJ
AD  - Center for Human Genome Variation, Duke University Medical Center, Durham, North 
      Carolina.
FAU - Daly, Ann K
AU  - Daly AK
AD  - Institute of Cellular Medicine, Newcastle University Medical School, Newcastle 
      upon Tyne, United Kingdom.
FAU - Aithal, Guruprasad P
AU  - Aithal GP
AD  - National Institute for Health Research Nottingham Digestive Diseases Biomedical 
      research Unit, Nottingham University Hospitals NHS Trust and University of 
      Nottingham, Nottingham, United Kingdom.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20140531
PL  - United States
TA  - Semin Liver Dis
JT  - Seminars in liver disease
JID - 8110297
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (HLA Antigens)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 2.3.1.88 (N-Terminal Acetyltransferases)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - EC 2.5.1.18 (Glutathione Transferase)
SB  - IM
MH  - ATP-Binding Cassette Transporters/genetics
MH  - Chemical and Drug Induced Liver Injury/*genetics/metabolism
MH  - Cytochrome P-450 Enzyme System/*genetics
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - Glucuronosyltransferase/genetics
MH  - Glutathione Transferase/genetics
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - Inactivation, Metabolic/genetics
MH  - N-Terminal Acetyltransferases/genetics
MH  - Oxidative Stress/genetics
MH  - Pharmacogenetics
EDAT- 2014/06/01 06:00
MHDA- 2015/02/24 06:00
CRDT- 2014/06/01 06:00
PHST- 2014/06/01 06:00 [entrez]
PHST- 2014/06/01 06:00 [pubmed]
PHST- 2015/02/24 06:00 [medline]
AID - 10.1055/s-0034-1375954 [doi]
PST - ppublish
SO  - Semin Liver Dis. 2014 May;34(2):123-33. doi: 10.1055/s-0034-1375954. Epub 2014 
      May 31.