AUTHOR=Sukasem Chonlaphat , Jantararoungtong Thawinee , Kuntawong Parnrat , Puangpetch Apichaya , Koomdee Napatrupron , Satapornpong Patompong , Supapsophon Patcharin , Klaewsongkram Jettanong , Rerkpattanapipat Ticha 

TITLE=HLA-B*58:01 for Allopurinol-Induced Cutaneous Adverse Drug Reactions: Implication for Clinical Interpretation in Thailand

JOURNAL=Frontiers in Pharmacology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2016.00186

DOI=10.3389/fphar.2016.00186

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> 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, <italic>n</italic> = 13), drug reaction with eosinophilia and systemic symptoms (DRESS, <italic>n</italic> = 10) and Maculopapular eruption (MPE; <italic>n</italic> = 7), conferred by <italic>HLA-B</italic><sup>*</sup><italic>58:01</italic> in a Thai population.</p><p><bold>Methods:</bold> This case-control association study compares 30 patients with allopurinol-induced CADR, allopurinol-tolerant control patients (<italic>n</italic> = 100), and a Thai general population (<italic>n</italic> = 1095). Patients' <italic>human leukocyte antigen type B (HLA-B)</italic> alleles were genotyped by using a two-stage sequence-specific oligonucleotide probe system.</p><p><bold>Results:</bold> Of a total 30 patients with CADR due to allopurinol, 29 (96.7%) patients were found to be at least heterozygous for <italic>HLA-B</italic><sup>*</sup><italic>58:01</italic>, compared to only 4.0% in allopurinol-tolerant patients (<italic>p</italic> &lt; 0.001). Odds ratio (OR) for the association of <italic>HLA-B</italic><sup>*</sup><italic>58:01</italic> with allopurinol-induced CADR in this population was 696.0 (95% CI: 74.8–6475.0). The <italic>HLA-B</italic><sup>*</sup><italic>58:01</italic> allele was present in all patients with allopurinol-induced SJS-TEN (OR = 579.0, 95%CI: 29.5–11362.7, <italic>p</italic> &lt; 0.001) and DRESS (OR 430.3, 95%CI: 22.6–8958.9, <italic>p</italic> &lt; 0.001). Additionally, OR of <italic>HLA-B</italic><sup>*</sup><italic>58:01</italic> was highly significant in the allopurinol-induced MPE patients (OR 144.0, 95%CI: 13.9–1497.0, <italic>p</italic> &lt; 0.001).</p><p><bold>Conclusion:</bold> In this study we confirmed the association between <italic>HLAB</italic><sup>*</sup><italic>58:01</italic> and allopurinol-induced SJS-TEN in a Thai population. In addition, we identified an association between <italic>HLA-B</italic><sup>*</sup><italic>58:01</italic> and allopurinol-induced DRESS and MPE in this population. Therefore, <italic>HLA-B</italic><sup>*</sup><italic>58:01</italic> can be used as a pharmacogenetic marker for allopurinol-induced CADR including SJS-TEN, DRESS and MPE. These results suggest that screening for <italic>HLA-B</italic><sup>*</sup><italic>58:01</italic> alleles in patients who will be treated with allopurinol would be clinically helpful in preventing the risk of developing CARD in a Thai patients.</p><p><bold>Summary</bold><list list-type="bullet"><list-item><p>Regardless of phenotype, this is the first pharmacogenetic study of allopurinol-induced CADR in patients of Thai ancestry.</p></list-item><list-item><p>In this study we confirmed the association between <italic>HLA-B</italic><sup>*</sup><italic>58:01</italic> and allopurinol-induced SJS-TEN, DRESS, and MPE in Thai population.</p></list-item><list-item><p>Regarding to our findings, the pharmacogenetic interpretation could be generalized to drug hypersensitivity including DRESS, SJS-TEN, and MPE.</p></list-item></list></p>