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HLA-B*58:01 等位基因与汉族人群别嘌醇诱导的轻中度和重度皮肤不良反应风险增加相关。

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

机构信息

Huashan Hospital, Fudan University, Shanghai, China.

出版信息

Pharmacogenomics. 2012 Jul;13(10):1193-201. doi: 10.2217/pgs.12.89.

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-B58:01 with allopurinol-induced severe cADRs was identified. This study investigated the predisposition to different types of allopurinol-cADRs conferred by HLA-B5801 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-B58:01, 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-B58:01. 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-B58:01 allele were observed. The results indicated that the prospective use of a genetic test of HLA-B58:01 might reduce the prevalence of allopurinol-induced cADRs. Original submitted 7 March 2012; Revision submitted 21 May 2012.

摘要

目的

别嘌醇作为一种有效的尿酸降低药物被广泛应用,是引起皮肤药物不良反应(cADR)最常见的原因之一。最近,研究发现 HLA-B58:01 与别嘌醇引起的严重 cADR 密切相关。本研究旨在探讨 HLA-B58:01 等位基因在中国汉族人群中对不同类型别嘌醇诱导的 cADR 的易感性。

患者和方法

2008 年至 2011 年,对 38 例不同类型别嘌醇诱导的 cADR 患者进行 HLA-B 基因分型。

结果

所有别嘌醇诱导的 cADR 患者均携带 HLA-B58:01,而在别嘌醇耐受患者中仅 11.11%(7/63)携带该基因型(比值比[OR] = 580.07;p < 0.0001),在人类 MHC 数据库(dbMHC)的汉族人群中仅 13.99%(80/572)携带该基因型(OR:471.09;p < 0.0001)。每种类型的别嘌醇诱导的 cADR 均与 HLA-B58:01 呈显著相关。特别是,HLA-B*58:01 患者发生别嘌醇诱导的斑丘疹性皮疹的风险显著增加(OR:339.00;p < 0.0001)。

结论

本研究观察到轻、重度别嘌醇诱导的 cADR 与 HLA-B58:01 等位基因密切相关。结果表明,前瞻性使用 HLA-B58:01 基因检测可能会降低别嘌醇诱导的 cADR 的发生率。

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