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Impact 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...

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Autores principales: Wu, Ran, Cheng, Yi-ju, Zhu, Li-li, Yu, Lei, Zhao, Xue-ke, Jia, Min, Wen, Chang-hui, Long, Xing-zhen, Tang, Ting, He, Ai-juan, Zeng, Yi-yan, Ma, Zun-feng, Zheng, Zhi, Ni, Mu-zi, Cai, Gong-jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348437/
https://www.ncbi.nlm.nih.gov/pubmed/27835909
http://dx.doi.org/10.18632/oncotarget.13250
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author Wu, Ran
Cheng, Yi-ju
Zhu, Li-li
Yu, Lei
Zhao, Xue-ke
Jia, Min
Wen, Chang-hui
Long, Xing-zhen
Tang, Ting
He, Ai-juan
Zeng, Yi-yan
Ma, Zun-feng
Zheng, Zhi
Ni, Mu-zi
Cai, Gong-jing
author_facet Wu, Ran
Cheng, Yi-ju
Zhu, Li-li
Yu, Lei
Zhao, Xue-ke
Jia, Min
Wen, Chang-hui
Long, Xing-zhen
Tang, Ting
He, Ai-juan
Zeng, Yi-yan
Ma, Zun-feng
Zheng, Zhi
Ni, Mu-zi
Cai, Gong-jing
author_sort Wu, Ran
collection PubMed
description 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 inconsistency, we conducted a meta-analysis of 21 pharmacogenetic studies, including 551 patients with allopurinol-induced CADRs, and 2,370 allopurinol-tolerant controls as well as 9,592 healthy volunteers. The summary OR for allopurinol-induced CADRs among HLA-B*58:01 carriers was 82.77 (95% CI: 41.63 – 164.58, P < 10(−5)) and 100.87 (95% CI: 63.91 – 159.21, P < 10(−5)) in matched and population based studies, respectively. Significant results were also observed when stratified by outcomes and ethnicity. Furthermore, the summary estimates for quantitative analysis of HLA-B*58:01 allele carriers in allopurinol-induced CADRs screening were as follows: sensitivity, 0.93 (95% CI: 0.85 – 0.97); specificity, 0.89 (95% CI: 0.87 – 0.91); positive likelihood ratio, 8.24 (95% CI: 6.92 – 9.81); negative likelihood ratio, 0.084 (95% CI: 0.039 – 0.179); and diagnostic odds ratio, 98.59 (95% CI: 43.31 – 224.41). The AUSROC was 0.92 (95% CI: 0.89–0.94), indicating the high diagnostic performance. Our results indicated that allopurinol–SCAR is strongly associated with HLA-B*58:01, and HLA-B*58:01 is a highly specific and effective genetic marker for the detection allopurinol-induced CADRs, especially for Asian descents.
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spelling pubmed-53484372017-03-31 Impact of HLA-B*58:01 allele and allopurinol-induced cutaneous adverse drug reactions: evidence from 21 pharmacogenetic studies Wu, Ran Cheng, Yi-ju Zhu, Li-li Yu, Lei Zhao, Xue-ke Jia, Min Wen, Chang-hui Long, Xing-zhen Tang, Ting He, Ai-juan Zeng, Yi-yan Ma, Zun-feng Zheng, Zhi Ni, Mu-zi Cai, Gong-jing Oncotarget Research Paper 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 inconsistency, we conducted a meta-analysis of 21 pharmacogenetic studies, including 551 patients with allopurinol-induced CADRs, and 2,370 allopurinol-tolerant controls as well as 9,592 healthy volunteers. The summary OR for allopurinol-induced CADRs among HLA-B*58:01 carriers was 82.77 (95% CI: 41.63 – 164.58, P < 10(−5)) and 100.87 (95% CI: 63.91 – 159.21, P < 10(−5)) in matched and population based studies, respectively. Significant results were also observed when stratified by outcomes and ethnicity. Furthermore, the summary estimates for quantitative analysis of HLA-B*58:01 allele carriers in allopurinol-induced CADRs screening were as follows: sensitivity, 0.93 (95% CI: 0.85 – 0.97); specificity, 0.89 (95% CI: 0.87 – 0.91); positive likelihood ratio, 8.24 (95% CI: 6.92 – 9.81); negative likelihood ratio, 0.084 (95% CI: 0.039 – 0.179); and diagnostic odds ratio, 98.59 (95% CI: 43.31 – 224.41). The AUSROC was 0.92 (95% CI: 0.89–0.94), indicating the high diagnostic performance. Our results indicated that allopurinol–SCAR is strongly associated with HLA-B*58:01, and HLA-B*58:01 is a highly specific and effective genetic marker for the detection allopurinol-induced CADRs, especially for Asian descents. Impact Journals LLC 2016-11-09 /pmc/articles/PMC5348437/ /pubmed/27835909 http://dx.doi.org/10.18632/oncotarget.13250 Text en Copyright: © 2016 Wu et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Wu, Ran
Cheng, Yi-ju
Zhu, Li-li
Yu, Lei
Zhao, Xue-ke
Jia, Min
Wen, Chang-hui
Long, Xing-zhen
Tang, Ting
He, Ai-juan
Zeng, Yi-yan
Ma, Zun-feng
Zheng, Zhi
Ni, Mu-zi
Cai, Gong-jing
Impact of HLA-B*58:01 allele and allopurinol-induced cutaneous adverse drug reactions: evidence from 21 pharmacogenetic studies
title Impact of HLA-B*58:01 allele and allopurinol-induced cutaneous adverse drug reactions: evidence from 21 pharmacogenetic studies
title_full Impact of HLA-B*58:01 allele and allopurinol-induced cutaneous adverse drug reactions: evidence from 21 pharmacogenetic studies
title_fullStr Impact of HLA-B*58:01 allele and allopurinol-induced cutaneous adverse drug reactions: evidence from 21 pharmacogenetic studies
title_full_unstemmed Impact of HLA-B*58:01 allele and allopurinol-induced cutaneous adverse drug reactions: evidence from 21 pharmacogenetic studies
title_short Impact of HLA-B*58:01 allele and allopurinol-induced cutaneous adverse drug reactions: evidence from 21 pharmacogenetic studies
title_sort impact of hla-b*58:01 allele and allopurinol-induced cutaneous adverse drug reactions: evidence from 21 pharmacogenetic studies
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348437/
https://www.ncbi.nlm.nih.gov/pubmed/27835909
http://dx.doi.org/10.18632/oncotarget.13250
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