Impact of HLA-B*58:01 allele and allopurinol-induced cutaneous adverse drug reactions: evidence from 21 pharmacogenetic studies
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Ran Wu1,*, Yi-ju Cheng2,3,*, Li-li Zhu4, Lei Yu5, Xue-ke Zhao6, Min Jia1, Chang-hui Wen1, Xing-zhen Long1, Ting Tang1, Ai-juan He1, Yi-yan Zeng1, Zun-feng Ma1, Zhi Zheng3, Mu-zi Ni3, Gong-jing Cai3
1Department of Dermatology, The First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine, Guiyang 550000, Guizhou, China
2Department of Respiratory Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China
3Department of Respiratory Medicine, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang 550014, Guizhou, China
4Blood Transfusion Department, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang 550014, Guizhou, China
5Prenatal Diagnostic Center, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China
6Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China
*These authors have contributed equally to this work
Lei Yu, email: [email protected]
Min Jia, email: [email protected]
Keywords: allopurinol, cutaneous adverse drug reactions, HLA-B*58:01, diagnosis, meta-analysis
Received: July 28, 2016 Accepted: October 27, 2016 Published: November 09, 2016
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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