title: Genetic markers associated with cutaneous adverse drug reactions to allopurinol: a systematic review.
abstract: Pharmacogenomic markers in the HLA coding genes have been associated with drug hypersensitivity of multiple drugs, including allopurinol. In this systematic review, we summarize the pharmacogenomic evidence available regarding allopurinol-induced cutaneous adverse drug reactions (cADRs). We found that the HLA-B*5801 allele was significantly associated with the risk of severe cADRs in the Han Chinese, Korean, Thai, Japanese and European populations. The association between less severe cADRs and HLA-B*5801 was less consistent. All SNPs identified in genome-wide association studies of common variants were also located in or nearby HLA-B*5801. Future studies should focus on more common but less severe allopurinol-induced cADRs, as well as the potential role of rare variants as predictors of these cADRs.
authors.affiliation: 1Faculty of Pharmacy, Université de Montréal, 2900 Boulevard Edouard-Montpetit, Montreal QC H3T 1J4, Canada.
authors.forename: Samantha
authors.initials: S
authors.lastname: Jarjour
authors.affiliation: 1Faculty of Pharmacy, Université de Montréal, 2900 Boulevard Edouard-Montpetit, Montreal QC H3T 1J4, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Barrette
authors.affiliation: 2Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Canada.
authors.forename: Valérie
authors.initials: V
authors.lastname: Normand
authors.affiliation: 3Faculty of Medicine, Université de Montréal, Montreal, Canada.|4Montreal Heart Institute, Research Center, 5000 Belanger Street, Montreal, Quebec H1T 1C8, Canada.
authors.forename: Jean Lucien
authors.initials: JL
authors.lastname: Rouleau
authors.affiliation: 2Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Canada.|3Faculty of Medicine, Université de Montréal, Montreal, Canada.|4Montreal Heart Institute, Research Center, 5000 Belanger Street, Montreal, Quebec H1T 1C8, Canada.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dubé
authors.affiliation: 1Faculty of Pharmacy, Université de Montréal, 2900 Boulevard Edouard-Montpetit, Montreal QC H3T 1J4, Canada.|2Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Canada.|4Montreal Heart Institute, Research Center, 5000 Belanger Street, Montreal, Quebec H1T 1C8, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: de Denus
mesh_terms: D000493:Allopurinol / Q000009:adverse effects*; D003875:Drug Eruptions / Q000175:diagnosis* / Q000235:genetics*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000235:genetics; D005819:Genetic Markers / Q000187:drug effects / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods / Q000639:trends; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods / Q000639:trends; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D005819:Genetic Markers; D006680:HLA Antigens; D000493:Allopurinol
keywords: HLA; Stevens–Johnson syndrome; adverse reaction; allopurinol; drug-induced hypersensitivity syndrome; pharmacogenomics; rash; safety; toxic epidermal necrolysis