Huashan Hospital, Fudan University, Shanghai, China.
Pharmacogenomics. 2012 Jul;13(10):1193-201. doi: 10.2217/pgs.12.89.
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.
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).
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.
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。
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。
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)。
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。