Jerram Samuel T, Leslie Richard David
Bart's and the London School of Medicine and Dentistry, QMUL, London E1 2AT, UK.
Genes (Basel). 2017 Aug 22;8(8):209. doi: 10.3390/genes8080209.
Type 1 diabetes (T1D) is classically characterised by the clinical need for insulin, the presence of disease-associated serum autoantibodies, and an onset in childhood. The disease, as with other autoimmune diseases, is due to the interaction of genetic and non-genetic effects, which induce a destructive process damaging insulin-secreting cells. In this review, we focus on the nature of this interaction, and how our understanding of that gene-environment interaction has changed our understanding of the nature of the disease. We discuss the early onset of the disease, the development of distinct immunogenotypes, and the declining heritability with increasing age at diagnosis. Whilst Human Leukocyte Antigens (HLA) have a major role in causing T1D, we note that some of these HLA genes have a protective role, especially in children, whilst other non-HLA genes are also important. In adult-onset T1D, the disease is often not insulin-dependent at diagnosis, and has a dissimilar immunogenotype with reduced genetic predisposition. Finally, we discuss the putative nature of the non-genetic factors and how they might interact with genetic susceptibility, including preliminary studies of the epigenome associated with T1D.
1型糖尿病（T1D）的典型特征是临床上需要胰岛素、存在与疾病相关的血清自身抗体以及在儿童期发病。与其他自身免疫性疾病一样，该疾病是由遗传和非遗传效应的相互作用引起的，这些效应会引发一个破坏胰岛素分泌细胞的过程。在本综述中，我们重点关注这种相互作用的本质，以及我们对这种基因-环境相互作用的理解如何改变了我们对该疾病本质的认识。我们讨论了疾病的早期发病、不同免疫基因型的发展以及随着诊断年龄的增加遗传度的下降。虽然人类白细胞抗原（HLA）在引发T1D中起主要作用，但我们注意到其中一些HLA基因具有保护作用，尤其是在儿童中，而其他非HLA基因也很重要。在成人发病的T1D中，疾病在诊断时通常不依赖胰岛素，并且具有不同的免疫基因型，遗传易感性降低。最后，我们讨论了非遗传因素的假定本质以及它们可能如何与遗传易感性相互作用，包括与T1D相关的表观基因组的初步研究。
