Diabetes in Population Isolates: Lessons from Greenland.
Diabetes in Population Isolates: Lessons from Greenland.
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DOI：
10.1900/rds.2015.12.320
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发表时间：
2015-09-01
期刊：
影响因子：
--
通讯作者：
Hansen, Torben
中科院分区：
文献类型：
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作者：
Grarup, Niels;Moltke, Ida;Hansen, Torben
2型糖尿病（T2D）是全球范围内日益严重的健康问题，在特定亚群和祖先群体中发生率特别高。T2D的高患病率是由生活方式和遗传易感性的改变引起的。大量的研究试图在欧洲人和亚洲人等大型开放人群中确定T2D的遗传决定因素。然而，群体分离株中T2D的研究正受到关注，因为它们在遗传疾病研究中提供了几个优于开放群体的优势，包括增加的连锁不平衡，同质环境暴露和增加的等位基因频率。我们最近在历史上与世隔绝的小型格陵兰人群中进行了一项研究，其中T2D的患病率已增加到10%以上。在这项研究中，我们确定了TBC1D4中一种常见的无义变体，它对葡萄糖刺激的血糖、血清胰岛素水平和T2D具有广泛的影响。该变体定义了非自身免疫性糖尿病的特定亚型，其特征在于餐后葡萄糖摄取减少和肌肉胰岛素抵抗。这些和其他最近在人群隔离中的发现说明了在遗传隔离人群中进行医学遗传学研究的价值。在这篇综述中，我们描述了一些进行遗传研究的T2D和相关的心脏代谢性状的人口隔离，如格陵兰岛的优势，我们讨论的潜力和前景，为未来的研究T2D在这个人口。
Type 2 diabetes (T2D) is an increasing health problem worldwide with particularly high occurrence in specific subpopulations and ancestry groups. The high prevalence of T2D is caused both by changes in lifestyle and genetic predisposition. A large number of studies have sought to identify the genetic determinants of T2D in large, open populations such as Europeans and Asians. However, studies of T2D in population isolates are gaining attention as they provide several advantages over open populations in genetic disease studies, including increased linkage disequilibrium, homogeneous environmental exposure, and increased allele frequency. We recently performed a study in the small, historically isolated Greenlandic population, in which the prevalence of T2D has increased to more than 10%. In this study, we identified a common nonsense variant in TBC1D4, which has a population-wide impact on glucose-stimulated plasma glucose, serum insulin levels, and T2D. The variant defines a specific subtype of non-autoimmune diabetes characterized by decreased post-prandial glucose uptake and muscular insulin resistance. These and other recent findings in population isolates illustrate the value of performing medical genetic studies in genetically isolated populations. In this review, we describe some of the advantages of performing genetic studies of T2D and related cardio-metabolic traits in a population isolate like the Greenlandic, and we discuss potentials and perspectives for future research into T2D in this population.