PMID- 21819236
OWN - NLM
STAT- MEDLINE
DCOM- 20120503
LR  - 20161125
IS  - 1545-4304 (Electronic)
IS  - 0362-1642 (Linking)
VI  - 52
DP  - 2012
TI  - Using genome-wide association studies to identify genes important in serious 
      adverse drug reactions.
PG  - 21-35
LID - 10.1146/annurev-pharmtox-010611-134743 [doi]
AB  - Genome-wide association (GWA) studies have detected novel associations for 
      serious, idiosyncratic, adverse drug reactions including liver toxicity, 
      hypersensitivity, skin rash, and myotoxicity. Human leukocyte antigen (HLA) 
      genotype has been established as an important predictor of susceptibility to 
      drug-induced liver injury, including injury with some drugs where immune-related 
      toxicity was not suspected previously. Similarly, GWA studies have shown a key 
      role for HLA genotype in susceptibility to carbamazepine-related skin rash and 
      hypersensitivity. HLA genotype is not a risk factor for all forms of drug-induced 
      liver injury or for myotoxicity or cardiotoxicity. For simvastatin-related 
      myotoxicity, a strong association with SLCO1B1, which encodes the hepatic statin 
      uptake transporter, has been detected. Genome-wide studies have not yet found 
      clear associations for drug-induced cardiotoxicity, but for 
      bisphosphonate-induced necrosis of the jaw, polymorphisms in the cytochrome P450 
      CYP2C8 may predict susceptibility. Larger GWA studies and whole-genome sequencing 
      may provide additional insights into all these toxicities.
FAU - Daly, Ann K
AU  - Daly AK
AD  - Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 
      4HH, United Kingdom. a.k.daly@ncl.ac.uk
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20110801
PL  - United States
TA  - Annu Rev Pharmacol Toxicol
JT  - Annual review of pharmacology and toxicology
JID - 7607088
RN  - 0 (HLA-A Antigens)
RN  - 33CM23913M (Carbamazepine)
RN  - AGG2FN16EV (Simvastatin)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (CYP2C8 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2C8)
SB  - IM
MH  - Aryl Hydrocarbon Hydroxylases/genetics/metabolism
MH  - Carbamazepine/adverse effects
MH  - Chemical and Drug Induced Liver Injury/genetics
MH  - Cytochrome P-450 CYP2C8
MH  - Drug-Related Side Effects and Adverse Reactions/*genetics
MH  - Exanthema/chemically induced/genetics
MH  - *Genetic Predisposition to Disease
MH  - *Genome, Human
MH  - Genome-Wide Association Study/*methods
MH  - Genotype
MH  - HLA-A Antigens/genetics
MH  - Humans
MH  - Hypersensitivity/genetics
MH  - Liver/drug effects
MH  - Pharmacogenetics/methods
MH  - Polymorphism, Genetic
MH  - Risk Factors
MH  - Simvastatin/adverse effects
EDAT- 2011/08/09 06:00
MHDA- 2012/05/04 06:00
CRDT- 2011/08/09 06:00
PHST- 2011/08/09 06:00 [entrez]
PHST- 2011/08/09 06:00 [pubmed]
PHST- 2012/05/04 06:00 [medline]
AID - 10.1146/annurev-pharmtox-010611-134743 [doi]
PST - ppublish
SO  - Annu Rev Pharmacol Toxicol. 2012;52:21-35. doi: 
      10.1146/annurev-pharmtox-010611-134743. Epub 2011 Aug 1.