HLA-B*58:01 for Allopurinol-Induced Cutaneous Adverse Drug Reactions: Implication for Clinical Interpretation in Thailand
نویسندگان
چکیده
BACKGROUND The aim of this study was to investigate the predisposition to different types of allopurinol-induced cutaneous adverse drug reactions (CADR), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN; SJS-TEN, n = 13), drug reaction with eosinophilia and systemic symptoms (DRESS, n = 10) and Maculopapular eruption (MPE; n = 7), conferred by HLA-B (*) 58:01 in a Thai population. METHODS This case-control association study compares 30 patients with allopurinol-induced CADR, allopurinol-tolerant control patients (n = 100), and a Thai general population (n = 1095). Patients' human leukocyte antigen type B (HLA-B) alleles were genotyped by using a two-stage sequence-specific oligonucleotide probe system. RESULTS Of a total 30 patients with CADR due to allopurinol, 29 (96.7%) patients were found to be at least heterozygous for HLA-B (*) 58:01, compared to only 4.0% in allopurinol-tolerant patients (p < 0.001). Odds ratio (OR) for the association of HLA-B (*) 58:01 with allopurinol-induced CADR in this population was 696.0 (95% CI: 74.8-6475.0). The HLA-B (*) 58:01 allele was present in all patients with allopurinol-induced SJS-TEN (OR = 579.0, 95%CI: 29.5-11362.7, p < 0.001) and DRESS (OR 430.3, 95%CI: 22.6-8958.9, p < 0.001). Additionally, OR of HLA-B (*) 58:01 was highly significant in the allopurinol-induced MPE patients (OR 144.0, 95%CI: 13.9-1497.0, p < 0.001). CONCLUSION In this study we confirmed the association between HLAB (*) 58:01 and allopurinol-induced SJS-TEN in a Thai population. In addition, we identified an association between HLA-B (*) 58:01 and allopurinol-induced DRESS and MPE in this population. Therefore, HLA-B (*) 58:01 can be used as a pharmacogenetic marker for allopurinol-induced CADR including SJS-TEN, DRESS and MPE. These results suggest that screening for HLA-B (*) 58:01 alleles in patients who will be treated with allopurinol would be clinically helpful in preventing the risk of developing CARD in a Thai patients. Summary Regardless of phenotype, this is the first pharmacogenetic study of allopurinol-induced CADR in patients of Thai ancestry.In this study we confirmed the association between HLA-B (*) 58:01 and allopurinol-induced SJS-TEN, DRESS, and MPE in Thai population.Regarding to our findings, the pharmacogenetic interpretation could be generalized to drug hypersensitivity including DRESS, SJS-TEN, and MPE.
منابع مشابه
HLA-B*58:01 allele is strongly associated with allopurinol-induced severe cutaneous adverse reactions in a Thai population
Background Allopurinol has been reported as the most frequent causes of SCARs (severe cutaneous adverse reactions) in Thailand. Recent publications have shown that HLAB*58:01 allele is a strong marker for allopurinol-induced SJS/TEN (Stevens-Johnson syndrome/toxic epidermal necrolysis). The aim of this study was to clarify the association of allopurinol-induced SCARs with the HLA-B*58:01 allele...
متن کاملComparison between the HLA-B∗58 : 01 Allele and Single-Nucleotide Polymorphisms in Chromosome 6 for Prediction of Allopurinol-Induced Severe Cutaneous Adverse Reactions
Severe cutaneous adverse drug reactions (SCARs) are life-threatening reactions. The strong association between the HLA-B∗58 : 01 allele and allopurinol-induced SCARs is well recognized. Screening for HLA-B∗58 : 01 allele before prescribing allopurinol in some populations has been recommended. Several single-nucleotide polymorphisms (SNPs) in chromosome 6 have been found to be tightly linked wit...
متن کاملA prospective study of HLA*B-5801 genotyping in preventing allopurinol- induced severe cutaneous adverse reactions
Background Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Allopurinol-induced SCAR is strongly associated with the HLA-B*58:01 allele. We sought to prevent allopurinol-induced SCAR by using HLA-B*58:01...
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Allopurinol (ALP) hypersensitivity is a major cause of severe cutaneous adverse reactions and is strongly associated with the HLA-B*58:01 allele. However, it can occur in the absence of this allele with identical clinical manifestations. The immune mechanism of ALP-induced severe cutaneous adverse reactions is poorly understood, and the T cell-reactivity pattern in patients with or without the ...
متن کاملImpact of HLA-B*58:01 allele and allopurinol-induced cutaneous adverse drug reactions: evidence from 21 pharmacogenetic studies
Allopurinol is widely used for hyperuricemia and gouty arthritis, but is associated with cutaneous adverse drug reactions (CADRs). Recently, HLA-B*58:01 allele was identified as a strong genetic marker for allopurinol-induced CADRs in Han Chinese. However, the magnitude of association and diagnosis value of HLA-B*58:01 in allopurinol-induced CADRs remain inconclusive. To investigate this incons...
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