title: A human leukocyte antigen locus haplotype confers risk for allopurinol-related adverse effects in Caucasian patients with gout.
abstract: A human leukocyte antigen haplotype comprising six single-nucleotide polymorphisms (SNPs) confers risk for allopurinol hypersensitivity syndrome in Caucasians. The objective of the current study was to test for association of this haplotype with other, less severe adverse effects (AEs) of allopurinol therapy in a large New Zealand gout cohort. A total of 626 Caucasian and 766 Polynesian patients were genotyped for six SNPs (rs2844665, rs9263715, rs3130931, rs3130501, rs3094188, rs9469003) using TaqMan SNP assays. The CACGAC haplotype occurred at a frequency of 0.018 in Caucasians and 0.009 in Polynesians. The CACGAC haplotype occurred at a significantly higher frequency in Caucasian patients who experienced allopurinol-related AEs (13.3 vs. 1.7%, P=8.9e-06, odds ratio=8.9, 95% confidence interval 2.8-27.9), but it was not associated with overall allopurinol toxicity in Polynesians (P>0.05). Our study is the first to demonstrate the potential utility of this six-SNP haplotype as a predictor of milder allopurinol AEs.
authors.affiliation: Departments of aSurgical Sciences bBiochemistry, Dunedin School of Medicine, University of Otago, Dunedin cWellington Regional Rheumatology Unit, Hutt Hospital, Lower Hutt dDepartment of Medicine, University of Auckland, Auckland eDepartment of Medicine, University of Otago, Wellington fDepartment of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Roberts
authors.forename: Mary C
authors.initials: MC
authors.lastname: Wallace
authors.forename: Andrew
authors.initials: A
authors.lastname: Harrison
authors.forename: Nicola
authors.initials: N
authors.lastname: Dalbeth
authors.forename: Tony R
authors.initials: TR
authors.lastname: Merriman
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Stamp
mesh_terms: D000493:Allopurinol / Q000009:adverse effects*; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006073:Gout / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D011114:Polynesia; D012307:Risk Factors; D044465:White People / Q000235:genetics*
chemical_list: D006680:HLA Antigens; D000493:Allopurinol