Mehers Kay L, Gillespie Kathleen M
Medical School Unit, Southmead Hospital, Bristol BS105NB, UK.
Br Med Bull. 2008;88(1):115-29. doi: 10.1093/bmb/ldn045.
Type 1 diabetes (T1D) is characterized by autoimmune destruction of insulin-producing beta-cells in the pancreas resulting from the action of environmental factors on genetically predisposed individuals. The increasing incidence over recent decades remains unexplained, but the capacity of identifying infants at highest genetic risk has become an increasing requirement for potential therapeutic intervention trials.
Literature searches on T1D and genes were carried out, and key papers since the 1970s were highlighted for inclusion in this review.
Early genetic studies identified the most important region for genetic susceptibility to T1D-the human leukocyte antigen genes on chromosome 6; later shown to contribute approximately half of the genetic determination of T1D. The other half is made up of multiple genes, each having a limited individual impact on genetic susceptibility.
Historically, there have been many controversial genetic associations with T1D, mostly caused by underpowered case-control studies but these are now decreasing in frequency. AREAS OF GROWTH: The functional effect of each gene associated with T1D must be investigated to determine its usefulness both in risk assessment and as a potential therapeutic target.
Recently identified copy number variants in DNA and epigenetic modifications (heritable changes not associated with changes in the DNA sequence) are also likely to play a role in genetic susceptibility to T1D.
1型糖尿病（T1D）的特征是胰腺中产生胰岛素的β细胞因环境因素作用于遗传易感性个体而发生自身免疫性破坏。近几十年来发病率不断上升，原因尚不明，但识别出遗传风险最高的婴儿的能力，对于潜在的治疗干预试验而言，已变得愈发必要。
对T1D和基因进行了文献检索，并着重列出了自20世纪70年代以来的关键论文以纳入本综述。
早期的遗传学研究确定了T1D遗传易感性最重要的区域——6号染色体上的人类白细胞抗原基因；后来发现该基因对T1D遗传决定作用约占一半。另一半则由多个基因组成，每个基因对遗传易感性的个体影响有限。
历史上，有许多与T1D存在争议的遗传关联，大多是由病例对照研究样本量不足导致的，但如今此类情况的发生频率正在降低。
必须研究与T1D相关的每个基因的功能效应，以确定其在风险评估和作为潜在治疗靶点方面的效用。
最近在DNA中发现的拷贝数变异和表观遗传修饰（与DNA序列变化无关的可遗传变化）也可能在T1D的遗传易感性中起作用。
