Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908-0717, USA.
Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908-0717, USA.
Curr Opin Genet Dev. 2018 Jun;50:7-16. doi: 10.1016/j.gde.2018.01.006. Epub 2018 Feb 14.
Type 1 diabetes is the most common autoimmune disorder in childhood, characterized by the development of autoimmunity through unknown environmental insults in genetically susceptible individuals. There are now over 50 regions of the genome that harbor type 1 diabetes susceptibility genes, with much of the genetic risk now well-defined in youth of Northern European ancestry. The impact of these genetic variants on initiation and progression of the autoimmune process (islet autoimmunity) is now being understood; however, studies are only now being conducted to understand the function of the variants associated with type 1 diabetes risk. The characteristics of genetic risk of type 1 diabetes across the age spectrum suggests extensive complexity in biological and environmental mechanisms. We propose that both genetic and environmental factors attributed to type 1 and type 2 diabetes may contribute to beta-cell death through multiple mechanisms, leading to the clinical outcome of type 1 diabetes.
1 型糖尿病是儿童中最常见的自身免疫性疾病,其特征是在遗传易感个体中,通过未知的环境损伤而发生自身免疫。现在已经确定了超过 50 个基因组区域存在 1 型糖尿病易感基因,北欧血统的年轻人中,大部分遗传风险已经明确。这些遗传变异对自身免疫过程(胰岛自身免疫)的启动和进展的影响现在已经被理解;然而,目前仅开展了一些研究来理解与 1 型糖尿病风险相关的变异的功能。1 型糖尿病在年龄谱上的遗传风险特征表明,其在生物学和环境机制方面存在广泛的复杂性。我们提出,与 1 型和 2 型糖尿病相关的遗传和环境因素可能通过多种机制导致β细胞死亡,从而导致 1 型糖尿病的临床结局。