Maggo Simran Ds, Chua Eng Wee, Chin Paul, Cree Simone, Pearson John, Doogue Matthew, Kennedy Martin A
Research Fellow, Carney Centre for Pharmacogenomics and Department of Pathology, University of Otago, Christchurch.
Lecturer, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
N Z Med J. 2017 Dec 1;130(1466):62-69.
A multitude of factors can affect drug response in individuals. It is now well established that variations in genes, especially those coding for drug metabolising enzymes, can alter the pharmacokinetic and/or pharmacodynamic profile of a drug, impacting on efficacy and often resulting in drug-induced toxicity. The UDRUGS study is an initiative from the Carney Centre for Pharmacogenomics to biobank DNA and store associated clinical data from patients who have suffered rare and/or serious adverse drug reactions (ADRs). The aim is to provide a genetic explanation of drug-induced ADRs using methods ranging from Sanger sequencing to whole exome and whole genome sequencing. Participants for the UDRUGS study are recruited from various sources, mainly via referral through clinicians working in Canterbury District Health Board, but also from district health boards across New Zealand. Participants have also self-referred to us from word-of-mouth communication between participants. We have recruited various ADRs across most drug classes. Where possible, we have conducted genetic analyses in single or a cohort of cases to identify known and novel genetic association(s) to offer an explanation to why the ADR occurred. Any genetic results relevant to the ADR are communicated back to the referring clinician and/or participant. In conclusion, we have developed a programme for studying the genetic basis of severe, rare or unusual ADR cases resulting from pharmacological treatment. Genomic analyses could eventually identify most genetic variants that predispose to ADRs, enabling a priori detection of such variants with high throughput DNA tests.
众多因素会影响个体对药物的反应。现在已经明确，基因变异，尤其是那些编码药物代谢酶的基因变异，会改变药物的药代动力学和/或药效学特征，影响疗效并常常导致药物诱导的毒性。UDRUGS研究是卡尼药物基因组学中心发起的一项倡议，旨在建立生物样本库，存储患有罕见和/或严重药物不良反应（ADR）患者的DNA及相关临床数据。其目的是使用从桑格测序到全外显子组和全基因组测序等方法，为药物诱导的ADR提供遗传学解释。UDRUGS研究的参与者来自各种渠道，主要是通过坎特伯雷地区卫生局的临床医生转诊，但也有来自新西兰各地的地区卫生局。参与者也通过参与者之间的口碑相传主动联系我们。我们招募了涉及大多数药物类别的各种ADR。在可能的情况下，我们对单个病例或一组病例进行了基因分析，以确定已知和新的基因关联，从而解释ADR发生的原因。任何与ADR相关的基因结果都会反馈给转诊的临床医生和/或参与者。总之，我们已经制定了一个项目，用于研究药物治疗导致的严重、罕见或异常ADR病例的遗传基础。基因组分析最终可能会识别出大多数易导致ADR的基因变异，从而能够通过高通量DNA检测对这些变异进行先验检测。
