Genetic association studies to detect adverse drug reactions: abacavir hypersensitivity as an example.
Abacavir hypersensitivity (ABC HSR) is a treatment-limiting adverse event associated with the use of the antiretroviral medicine, abacavir. The objective of the ABC HSR pharmacogenetics program was to identify clinically useful genetic risk factors to predict an individual patient's risk for ABC HSR. The major histocompatibility complex allele, HLA-B*5701, was identified retrospectively and confirmed with independent sample sets. The clinical utility of prospective HLA-B*5701 screening was demonstrated in a blinded randomized clinical trial and in open-label cohorts. Screening has been incorporated into clinical practice and the ABC HSR pharmacogenetics program has been highlighted as a success by pharmacogenetics researchers. Important lessons from this pharmacogenetics program will be discussed in this paper.
Hughes
Arlene R
AR
GlaxoSmithKline Genetics, 5 Moore Drive, PO Box 13398, Research Triangle Park, NC 27709, USA. arlene.r.hughes@gsk.com
Brothers
Cynthia H
CH
Mosteller
Michael
M
Spreen
William R
WR
Burns
Daniel K
DK
D015224:Dideoxynucleosides / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000235:genetics* / Q000401:mortality; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D010641:Phenotype; D011446:Prospective Studies; D012107:Research Design; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D000099227:Abacavir
D015224:Dideoxynucleosides; D015235:HLA-B Antigens; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir; C484830:HLA-B*57:01 antigen