PMID- 28695285
OWN - NLM
STAT- MEDLINE
DCOM- 20170929
LR  - 20220801
IS  - 1432-1211 (Electronic)
IS  - 0093-7711 (Linking)
VI  - 69
IP  - 8-9
DP  - 2017 Aug
TI  - The role of HLA genes in pharmacogenomics: unravelling HLA associated adverse 
      drug reactions.
PG  - 617-630
LID - 10.1007/s00251-017-1007-5 [doi]
AB  - Genetic polymorphism in the genes encoding the human leukocyte antigen (HLA) 
      molecules enables presentation of a wide range peptide ligands thus maximising 
      immune surveillance of pathogens. A consequence of the diversification of the HLA 
      Ag-binding pocket is the enhanced opportunity for off-target binding of small 
      drugs by HLA molecules, with subsequent immune reactivity. These potential 
      off-target interactions are 'set up' to generate T cell-mediated adverse drug 
      reactions even though the precise mechanisms of most HLA-drug interactions are 
      still poorly understood. The association between abacavir hypersensitivity 
      syndrome and HLA-B*57:01 is one exception that has been resolved at a molecular 
      and mechanistic level. Here, we explore the road to understanding the interaction 
      between abacavir and the HLA-B*57:01 molecule and review the current state of 
      understanding of interactions between other drugs and HLA molecules implicated in 
      adverse drug reactions, which appear to involve multiple mechanisms. The 
      continued expansion of the pharmacopoeia generates an imperative to understand 
      these interactions at the molecular level in order to prevent the continued 
      burden on individuals and the health care system.
FAU - Illing, Patricia T
AU  - Illing PT
AD  - Infection and Immunity Program & Department of Biochemistry and Molecular 
      Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, 
      Australia.
FAU - Purcell, Anthony W
AU  - Purcell AW
AD  - Infection and Immunity Program & Department of Biochemistry and Molecular 
      Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, 
      Australia.
FAU - McCluskey, James
AU  - McCluskey J
AD  - Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity, University of Melbourne, Parkville, VIC, 3010, Australia. 
      jamesm1@unimelb.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20170710
PL  - United States
TA  - Immunogenetics
JT  - Immunogenetics
JID - 0420404
RN  - 0 (HLA Antigens)
RN  - 0 (Haptens)
RN  - 33CM23913M (Carbamazepine)
RN  - 63CZ7GJN5I (Allopurinol)
SB  - IM
MH  - Allopurinol/adverse effects
MH  - Carbamazepine/adverse effects
MH  - Drug-Related Side Effects and Adverse Reactions/*genetics/immunology
MH  - HLA Antigens/*genetics
MH  - Haptens/immunology
MH  - Humans
MH  - *Pharmacogenetics
MH  - Polymorphism, Genetic
OTO - NOTNLM
OT  - Abacavir
OT  - Adverse drug reactions
OT  - Antigen processing and presentation
OT  - Human leukocyte antigen
OT  - Major histocompatibility complex
EDAT- 2017/07/12 06:00
MHDA- 2017/09/30 06:00
CRDT- 2017/07/12 06:00
PHST- 2017/05/29 00:00 [received]
PHST- 2017/05/29 00:00 [accepted]
PHST- 2017/07/12 06:00 [pubmed]
PHST- 2017/09/30 06:00 [medline]
PHST- 2017/07/12 06:00 [entrez]
AID - 10.1007/s00251-017-1007-5 [pii]
AID - 10.1007/s00251-017-1007-5 [doi]
PST - ppublish
SO  - Immunogenetics. 2017 Aug;69(8-9):617-630. doi: 10.1007/s00251-017-1007-5. Epub 
      2017 Jul 10.