HLA-B*58:01 allele is associated with augmented risk for both mild and severe cutaneous adverse reactions induced by allopurinol in Han Chinese

Author:

Cao Zhi-hao1,Wei Zhi-yun23,Zhu Qin-yuan1,Zhang Jun-yu2,Yang Lun3,Qin Sheng-ying3,Shao Li-yan3,Zhang Yi-ting2,Xuan Jie-kun3,Li Qiao-li2,Xu Jin-hua1,Xu Feng1,Ma Li1,Huang Hui-yuan1,Xing Qing-he4,Luo Xiao-qun5

Affiliation:

1. Huashan Hospital, Fudan University, Shanghai, China

2. Children’s Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, China

3. Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education), Bio-X Center, Shanghai Jiao Tong University, Shanghai, China

4. Children’s Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

5. 12 Wulumiqi Zhong Road, Jing’an District, Shanghai, China.

Abstract

Aim: Allopurinol is widely used as an effective urate-lowering drug and is one of the most frequent causes of cutaneous adverse drug reactions (cADRs). Recently, a strong association of HLA-B*58:01 with allopurinol-induced severe cADRs was identified. This study investigated the predisposition to different types of allopurinol-cADRs conferred by HLA-B*5801 in a Han population from mainland China. Patients & methods:HLA-B genotyping was performed on 38 Chinese patients with different types of allopurinol-cADRs from 2008 to 2011. Results: All the allopurinol-cADR patients carried HLA-B*58:01, in contrast with only 11.11% (7/63) in the allopurinol-tolerant patients (odds ratio [OR] = 580.07; p < 0.0001) and 13.99% (80/572) in a Han Chinese population from the human MHC database (dbMHC; OR: 471.09; p < 0.0001) carried the genotype. Each type of allopurinol cADRs revealed a statistically significant association with HLA-B*58:01. In particular, the risk of allopurinol-induced maculopapular eruption was significantly higher in patients with HLA-B*58:01 (OR: 339.00; p < 0.0001). Conclusion: The strong association of both the mild and severe types of allopurinol cADRs with the HLA-B*58:01 allele were observed. The results indicated that the prospective use of a genetic test of HLA-B*58:01 might reduce the prevalence of allopurinol-induced cADRs. Original submitted 7 March 2012; Revision submitted 21 May 2012

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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