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【Nature】Getting personal
NATURE REVIEWS | DRUG DISCOVERY VOLUME 6 | AUGUST 2007 | 587
The possibility of more widespread application of ‘personalized medicine’, in which therapy is tailored to factors such as an individual’s genetic make-up, has been on the horizon for years, but so far, translation of this concept to clinical practice has been limited. What might it take to change this situation?
个体化医疗有更广泛应用的可能，针对个体的遗传变异等因素制定治疗方案，这种设想已经有很多年了，但直到目前为止，把这个概念应用到临床实践中还有限。如何去改变这种状况呢？
This year marks the 150th anniversary of the birth of the British doctor Archibald Garrod, who coined the term ‘inborn error of metabolism’ to refer to monogenic diseases such as alkaptonuria — a disorder characterized by symptoms such as pigmented urine that is now known to be caused by the inheritance of two abnormal copies of the gene that encodes homogentisic acid oxidase. Garrod has also been credited with making the first proposal of a familial component in the variability of the effects of drugs, which might be considered to be the birth of the field of pharmacogenetics
今年是英国医生Archibald Garrod的150周年诞辰，Garrod首先用“先天性代谢缺陷”来指代单基因遗传的疾病如黑尿病等，这种疾病的症状是出现色素尿，目前已知是被编码尿黑酸氧化酶基因的两个异常的拷贝所造成的。Garrod首先提出家族性组成的遗传变异影响药物的作用，这可以被视为药理遗传学领域的诞生。
Now, several decades on from these ground-breaking proposals, it seems that the understanding of the genetic basis of diseases and of the responses to drugs is entering a new era. For example, as discussed in a news feature on page 590 of this issue, the past year has seen a flurry of genome-wide association studies that have identified genetic variants linked with various common complex diseases such as type 2 diabetes, rheumatoid arthritis and prostate cancer. Elucidating the genetic factors underlying such diseases poses a much greater challenge than that for monogenic diseases such as alkaptonuria, as these diseases are related to the complex interaction of multiple genes — each typically with a small effect — and environmental factors. Such challenges, however, are increasingly now being successfully tackled.
现在进入一个新的时代，从这些具有突破性意义的建议开始的几十年来，与遗传变异相关的疾病和对药物反应的认识有了新的认识。举例来说，在本期的的第590页讨论了这个问题，过去的一年里出现了一系列的全基因组的相关研究，已经确定的与遗传变异联系在一起的各复杂而常见的疾病有2型糖尿病，类风湿关节炎和前列腺肿瘤。阐明这些多基因遗传相关的疾病比单基因遗传的疾病如黑尿症等构成了更大的挑战，因为这些疾病是涉及到复杂的相互作用的多个基因和环境因素，每个相关的基因通常是一个小的影响。现在这些挑战越来越多的被成功解决。
The completion of the sequencing of the human genome at the start of this decade has been a key to this
success, but it is only recently that several other advances have begun to allow more of the potential of this genomic knowledge to be realized. In the case of genome-wide association studies, important information has also come from the cataloguing of genomic variations in the form of single nucleotide polymorphisms and data on their statistical relatedness from the HapMap project (http://www.hapmap.org). Coupling the availability of such information with increasingly powerful highthroughput technologies for genotyping has made the analysis of the potential linkage of up to 500,000 genetic variants with disease in thousands of subjects practically and financially feasible. As a result, a wide variety of clues — both expected and unexpected — about the genetic basis of disease are being revealed.
人类基因组测序在这个十年开始的时候完成，这是这项工作成功的关键，但是最近其他几个进步已经开始让这项工作有了更大的潜力，有关基因组的知识得以实现。在有关全基因组的研究中，关键的信息来自基因组编码的遗传变异，也就是单核苷酸多态性，相关的数据和统计的相关来自HapMap计划（http://www.hapmap.org）。整合这些资料与日益强大的高通量的基因分型技术，可以作出高达500000个的遗传变异与数以千计的疾病潜在联系的分析，在经济上也是是可行的。因此，各种各样的线索-预期和意想不到的-关于疾病的遗传基础信息正在出现。
As such knowledge is likely to grow rapidly with the completion of further genome-wide association
studies, also including those studying variations in drug response, a key question as always is how the knowledge might be translated into therapeutic applications. This question was the basis for a recent symposium entitled Personalized medicine: prospect or pipedream? organized by the Institute for Translational Medicine and Therapeutics (http://www.itmat.upenn.edu) in Philadelphia, USA, and supported by Nature Reviews Drug Discovery.
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作者:admin@医学,生命科学 2011-08-23 17:36
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