Cornejo-Garcia Jose A, Oussalah Abderrahim, Blanca Miguel, Gueant-Rodriguez Rosa-Maria, Mayorga Cristobalina, Waton Julie, Barbaud Annick, Gaeta Francesco, Romano Antonino, Gueant Jean-Louis
Faculte de Medecine, Batiment C 2eme etage, 9 avenue de la Foret de Haye - B.P. 184, 54505 Vandoeuvre- les-Nancy CEDEX, France.
Curr Pharm Des. 2016;22(45):6725-6733. doi: 10.2174/1381612822666160927114941.
Our knowledge of genetic predisposing factors of drug hypersensitivity reactions (DHRs) is still scarce. The analysis of the genetic basis of these reactions may contribute to dissect the underlying mechanisms. We will outline current knowledge of the genetic predictors of most common DHRs, including reactions to betalactam antibiotics (BLs), nonsteroidal anti-inflammatory drugs (NSAIDs) and biological agents. The predictors of DHRs to BLs are mostly linked to IgE-class switching, IgE pathway and atopy (IL4R, NOD2, LGALS3) in replicated candidate gene studies, and to antigen presentation (HLA-DRA) in the single replicated GWAS performed so far. The HLA-DRA variants are predictors of allergy to penicillins, but not to cephalosporins and they influence also the sensitization against prevalent allergens. The predictors of DHRs against NSAIDs are mostly linked to metabolism of eicosanoids (ALOX5, ALOX5AP, TBXAS1, PTGDR, CYSLTR1). Single nucleotide polymorphisms (SNPs) in genes involved in histamine biosynthesis and antigen presentation, HLA, could also have a role in DHRs against NSAIDs. The intriguing association of DHRs to NSAIDs with atopy should deserve further attention. Predictors of DHRs against asparaginase and other biological agents relate to antigen presentation (HLA-DRB1 and HLA-A alleles, respectively). The potential relationship of genetic predictors of DHRs with pathomechanisms also involved in environmental exposure and atopy highlights the need to perform GWAS in contrasted populations, taking into account world-wide variations of allele frequencies and contrasted situations of environmental exposure.
我们对药物超敏反应（DHRs）的遗传易感性因素的了解仍然有限。对这些反应的遗传基础进行分析可能有助于剖析其潜在机制。我们将概述目前对最常见DHRs的遗传预测指标的认识，包括对β-内酰胺类抗生素（BLs）、非甾体抗炎药（NSAIDs）和生物制剂的反应。在重复的候选基因研究中，DHRs对BLs的预测指标大多与IgE类别转换、IgE途径和特应性（IL4R、NOD2、LGALS3）相关，而在迄今为止进行的单次重复全基因组关联研究（GWAS）中，则与抗原呈递（HLA-DRA）相关。HLA-DRA变体是对青霉素过敏的预测指标，但不是对头孢菌素过敏的预测指标，它们也影响对常见过敏原的致敏作用。DHRs对NSAIDs的预测指标大多与类花生酸代谢（ALOX5、ALOX5AP、TBXAS1、PTGDR、CYSLTR1）相关。参与组胺生物合成和抗原呈递的基因（HLA）中的单核苷酸多态性（SNP）也可能在DHRs对NSAIDs的反应中起作用。DHRs与NSAIDs和特应性之间有趣的关联值得进一步关注。DHRs对天冬酰胺酶和其他生物制剂的预测指标分别与抗原呈递（HLA-DRB1和HLA-A等位基因）相关。DHRs的遗传预测指标与环境暴露和特应性中也涉及的发病机制之间的潜在关系凸显了在对比人群中进行GWAS的必要性，同时要考虑到等位基因频率的全球差异和环境暴露的对比情况。
