Szalai Csaba, Tölgyesi Gergely, Nagy Adrienne, Falus András
Heim Pál Gyermekkórház es Rendelointézet, Molekuláris Genetikai Laboratórium.
Orv Hetil. 2006 Jan 29;147(4):159-69.
One main area of pharmacogenomics is the discovery of new drugs and drug targets with molecular genetic or genomic methods; the other is the study of how genomic differences influence the variability in patients responses to drugs. In this review the authors summarise the most important results of this latter issue. Despite the availability of three major classes of therapeutic agents for asthma, it has been estimated that as many as half of asthmatic patients do not respond to treatment with beta2-agonists, leukotriene modifiers or inhaled corticosteroids. Moreover, in some individuals asthma therapy has been associated with serious adverse drug reactions. An estimated 60 to 80% of variability in individual responses to therapy may have genetic bases. All of the currently available data on asthma pharmacogenomics originated from genetic variations in genes of the drug treatment target or target pathways. Results of genetic association studies that investigate responses to beta2-agonist, leukotriene modifier and corticosteroid therapy will be summarised and recent findings in the literature highlighted. Although, at present pharmacogenomics can explain only a fraction of the adverse drug responses, hopefully these results mark the clinical use of genotyping at an individual level as adjunct to pharmacotherapy for asthma and many other diseases.
药物基因组学的一个主要领域是利用分子遗传学或基因组学方法发现新药物和药物靶点;另一个领域是研究基因组差异如何影响患者对药物反应的变异性。在本综述中,作者总结了后一个问题的最重要结果。尽管有三类主要的哮喘治疗药物,但据估计,多达一半的哮喘患者对β2激动剂、白三烯调节剂或吸入性糖皮质激素治疗无反应。此外,在一些个体中,哮喘治疗与严重的药物不良反应有关。据估计,个体对治疗反应的变异性中,60%至80%可能有遗传基础。目前所有关于哮喘药物基因组学的数据均源自药物治疗靶点或靶点途径基因的遗传变异。本文将总结关于β2激动剂、白三烯调节剂和糖皮质激素治疗反应的遗传关联研究结果,并突出文献中的最新发现。尽管目前药物基因组学只能解释一部分药物不良反应,但有望这些结果标志着在个体水平上进行基因分型作为哮喘及许多其他疾病药物治疗辅助手段的临床应用。