Vaxillaire Martine, Froguel Philippe
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8090, Institute of Biology and Pasteur Institute, Lille, France.
Endocr Rev. 2008 May;29(3):254-64. doi: 10.1210/er.2007-0024. Epub 2008 Apr 24.
Most valuable breakthroughs in the genetics of type 2 diabetes for the past two decades have arisen from candidate gene studies and familial linkage analysis of maturity-onset diabetes of the young (MODY), an autosomal dominant form of diabetes typically occurring before 25 years of age caused by primary insulin secretion defects. Despite its low prevalence, MODY is not a single entity but presents genetic, metabolic and clinical heterogeneity. MODY can result from mutations in at least six different genes encoding the glucose sensor enzyme glucokinase and transcription factors that participate in a regulatory network essential for adult beta-cell function. Additional genes have been described in other discrete phenotypes or syndromic forms of diabetes. Whereas common variants in the MODY genes contribute very modestly to type 2 diabetes susceptibility in adults, major findings emerging from the advent of genome-wide association studies will deliver an increasing number of genes and new pathways for the pathological events of the disease.
在过去二十年里，2型糖尿病遗传学领域最有价值的突破来自候选基因研究以及青年发病型成年糖尿病（MODY）的家族连锁分析。MODY是一种常染色体显性糖尿病，通常在25岁之前发病，由原发性胰岛素分泌缺陷引起。尽管MODY发病率较低，但它并非单一疾病，而是存在遗传、代谢和临床异质性。MODY可能由至少六个不同基因的突变导致，这些基因编码葡萄糖传感器酶葡萄糖激酶以及参与成年β细胞功能必需调控网络的转录因子。在其他离散型糖尿病表型或综合征型糖尿病中也发现了其他相关基因。虽然MODY基因中的常见变异对成人2型糖尿病易感性的影响很小，但全基因组关联研究带来的主要发现将揭示越来越多与该疾病病理事件相关的基因和新途径。
