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 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.
Department of Dermatology, The First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine, Guiyang 550000, Guizhou, China.
Ran
R
Wu
Department of Respiratory Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China.|Department of Respiratory Medicine, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang 550014, Guizhou, China.
Yi-Ju
YJ
Cheng
Blood Transfusion Department, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang 550014, Guizhou, China.
Li-Li
LL
Zhu
Prenatal Diagnostic Center, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China.
Lei
L
Yu
Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China.
Xue-Ke
XK
Zhao
Department of Dermatology, The First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine, Guiyang 550000, Guizhou, China.
Min
M
Jia
Department of Dermatology, The First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine, Guiyang 550000, Guizhou, China.
Chang-Hui
CH
Wen
Department of Dermatology, The First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine, Guiyang 550000, Guizhou, China.
Xing-Zhen
XZ
Long
Department of Dermatology, The First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine, Guiyang 550000, Guizhou, China.
Ting
T
Tang
Department of Dermatology, The First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine, Guiyang 550000, Guizhou, China.
Ai-Juan
AJ
He
Department of Dermatology, The First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine, Guiyang 550000, Guizhou, China.
Yi-Yan
YY
Zeng
Department of Dermatology, The First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine, Guiyang 550000, Guizhou, China.
Zun-Feng
ZF
Ma
Department of Respiratory Medicine, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang 550014, Guizhou, China.
Zhi
Z
Zheng
Department of Respiratory Medicine, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang 550014, Guizhou, China.
Mu-Zi
MZ
Ni
Department of Respiratory Medicine, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang 550014, Guizhou, China.
Gong-Jing
GJ
Cai
D000493:Allopurinol / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D003875:Drug Eruptions / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006074:Gout Suppressants / Q000009:adverse effects*; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D016017:Odds Ratio; D010597:Pharmacogenetics; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants; D018570:Risk Assessment; D012307:Risk Factors
D006074:Gout Suppressants; D015235:HLA-B Antigens; C500126:HLA-B*58:01 antigen; D000493:Allopurinol
HLA-B*58:01; allopurinol; cutaneous adverse drug reactions; diagnosis; meta-analysis