药学学报, 2013, 48(6): 799-808
引用本文:
王 青, 梅 虎, 张亚兰, 潘显超, 谭 文, 晁 丽. 遗传异质性药物毒副作用与HLA基因关联及分子机制研究进展[J]. 药学学报, 2013, 48(6): 799-808.
WANG Qing, MEI Hu, ZHANG Ya-lan, PAN Xian-chao, TAN Wen, CHAO Li. The associations between idiosyncratic adverse drug reactions and HLA alleles and their underlying mechanism[J]. Acta Pharmaceutica Sinica, 2013, 48(6): 799-808.

遗传异质性药物毒副作用与HLA基因关联及分子机制研究进展
王 青1, 梅 虎1, 2*, 张亚兰1, 潘显超1, 谭 文1, 晁 丽1
(重庆大学 1. 生物工程学院, 2. 生物流变科学与技术教育部重点实验室, 重庆 400044)
摘要:

随着高通量基因测序技术的发展, 全基因组关联分析 (genome-wide association study, GWAS) 被越来越多地应用到遗传异质性药物毒副作用 (adverse drug reactions, ADRs) 研究中。越来越多的研究发现: 遗传异质性ADRs与人类白细胞抗原 (human leukocyte antigen, HLA) 密切相关, 阿巴卡韦 (abacavir) HLA-B*5701、别嘌醇 (allopurinol) HLA-B*5801、卡马西平 (carbamazepine) HLA-B*1502等基因关联。针对上述基因关联现象, 相继提出半抗原理论、危险因子理论、P-I理论以及最新提出的自身免疫机制。本文就遗传异质性ADRsHLA基因关联及其机制研究的最新进展进行了详细综述。

关键词:   
The associations between idiosyncratic adverse drug reactions and HLA alleles and their underlying mechanism
Abstract:

With the advent of Twenty-First century, more and more genome-wide association studies (GWAS) showed that idiosyncratic adverse drug reactions (ADRs) were closely related with human leukocyte antigen (HLA) alleles, such as the associations of abacavir-HLA-B*5701, allopurinol-HLA-B*5801, and carbamazepine- HLA-B*1502, etc.  To explore the mechanisms of these idiosyncratic drug reactions, hapten hypothesis, danger signal hypothesis, pharmacological interaction (P-I) concept and autoimmune mechanism are proposed.  In this paper, recent GWAS studies on the HLA-mediated adverse drug reactions and underlying mechanism are reviewed in detail.

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