Florez Jose C
Simches Research Building-CPZN 5.250, 185 Cambridge Street, Diabetes Unit/Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
J Clin Endocrinol Metab. 2008 Dec;93(12):4633-42. doi: 10.1210/jc.2008-1345. Epub 2008 Sep 9.
Over the last few months, genome-wide association studies have contributed significantly to our understanding of the genetic architecture of type 2 diabetes. If and how this information will impact clinical practice is not yet clear.
Primary papers reporting genome-wide association studies in type 2 diabetes or establishing a reproducible association for specific candidate genes were compiled. Further information was obtained from background articles, authoritative reviews, and relevant meeting conferences and abstracts.
As many as 17 genetic loci have been convincingly associated with type 2 diabetes; 14 of these were not previously known, and most of them were unsuspected. The associated polymorphisms are common in populations of European descent but have modest effects on risk. These loci highlight new areas for biological exploration and allow the initiation of experiments designed to develop prediction models and test possible pharmacogenetic and other applications.
Although substantial progress in our knowledge of the genetic basis of type 2 diabetes is taking place, these new discoveries represent but a small proportion of the genetic variation underlying the susceptibility to this disorder. Major work is still required to identify the causal variants, test their role in disease prediction and ascertain their therapeutic implications.
在过去几个月里，全基因组关联研究对我们理解2型糖尿病的遗传结构做出了重大贡献。但这些信息是否以及如何影响临床实践尚不清楚。
收集了报告2型糖尿病全基因组关联研究或为特定候选基因建立可重复关联的主要论文。通过背景文章、权威综述以及相关会议和摘要获取了更多信息。
多达17个基因位点已被证实与2型糖尿病相关；其中14个此前未知，且大多数未被怀疑。相关的多态性在欧洲裔人群中很常见，但对风险的影响较小。这些基因位点为生物学探索指明了新领域，并使得开展旨在开发预测模型以及测试可能的药物遗传学及其他应用的实验成为可能。
尽管我们在2型糖尿病遗传基础的认识上取得了重大进展，但这些新发现仅占该疾病易感性潜在遗传变异的一小部分。仍需要开展大量工作来识别因果变异、测试它们在疾病预测中的作用并确定其治疗意义。
