PMID- 24694233
OWN - NLM
STAT- MEDLINE
DCOM- 20141124
LR  - 20191027
IS  - 1875-5453 (Electronic)
IS  - 1389-2002 (Linking)
VI  - 15
IP  - 2
DP  - 2014 Feb
TI  - Human leukocyte antigen (HLA) pharmacogenomic tests: potential and pitfalls.
PG  - 196-201
AB  - Adverse drug reactions involving a range of prescribed drugs and affecting the 
      skin, liver and other organs show strong associations with particular HLA 
      alleles. For some reactions, HLA typing prior to prescription, so that those 
      positive for the risk allele are not given the drug associated with the reaction, 
      shows high positive and negative predictive values. The best example of clinical 
      implementation relates to the hypersensitivity reaction induced by the anti-HIV 
      drug abacavir. When this reaction is phenotyped accurately, 100% of those who 
      develop it are positive for HLA-B*57:01. Drug regulators worldwide now recommend 
      genotyping for HLA-B*57:01 before abacavir is prescribed. Serious skin rashes 
      including Stevens-Johnson syndrome and toxic epidermal necrosis can be induced by 
      carbamazepine and other anticonvulsant drugs. In certain East Asians, these 
      reactions are significantly associated with HLA-B*15:02, and typing for this 
      allele is now recommended prior to carbamazepine prescription in these 
      populations. Other HLA associations have been described for skin rash induced by 
      carbamazepine, allopurinol and nevirapine and for liver injury induced by 
      flucloxacillin, amoxicillin-clavulanate, lapatanib, lumiracoxib and ticlopidine. 
      However, the predictive values for typing HLA alleles associated with these 
      adverse reactions are lower. Clinical implementation therefore seems unlikely. 
      Performing HLA typing is relatively complex compared with genotyping assays for 
      single nucleotide polymorphisms. With emphasis on HLA-B*57:01, the approaches 
      used commonly, including use of sequence-specific oligonucleotide PCR primers and 
      DNA sequencing are considered, together with their successful implementation. 
      Genotyping single nucleotide polymorphisms tagging HLA alleles is a simpler 
      alternative to HLA typing but appears insufficiently accurate for clinical use.
FAU - Daly, Ann K
AU  - Daly AK
AD  - Institute of Cellular Medicine, Newcastle University, Framlington Place, 
      Newcastle upon Tyne NE2 4HH, UK. a.k.daly@ncl.ac.uk.
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Curr Drug Metab
JT  - Current drug metabolism
JID - 100960533
RN  - 0 (DNA Primers)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B57 antigen)
SB  - IM
MH  - DNA Primers
MH  - Drug-Related Side Effects and Adverse Reactions/*genetics
MH  - Genetic Testing/methods
MH  - Genotype
MH  - HLA Antigens/*genetics
MH  - HLA-B Antigens/genetics
MH  - Humans
MH  - Pharmacogenetics/*methods
MH  - Polymorphism, Single Nucleotide
MH  - Predictive Value of Tests
MH  - Sequence Analysis, DNA/methods
EDAT- 2014/04/04 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/04/04 06:00
PHST- 2013/10/07 00:00 [received]
PHST- 2013/12/27 00:00 [revised]
PHST- 2014/01/21 00:00 [accepted]
PHST- 2014/04/04 06:00 [entrez]
PHST- 2014/04/04 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - CDM-59811 [pii]
AID - 10.2174/138920021502140327180733 [doi]
PST - ppublish
SO  - Curr Drug Metab. 2014 Feb;15(2):196-201. doi: 10.2174/138920021502140327180733.