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.
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