Serjeantson S W, Zimmet P
Baillieres Clin Endocrinol Metab. 1991 Sep;5(3):477-93. doi: 10.1016/s0950-351x(05)80143-0.
Family studies suggest a strong genetic component in the aetiology of non-insulin dependent diabetes (NIDDM), with evidence for a major gene of co-dominant or dominant effect. A gene-dosage effect, whereby diabetes develops earlier in people with two susceptibility genes than in those with one susceptibility gene is likely. The search for the diabetes gene has led to the cloning and characterization of many genes involved in controlling glucose homeostasis. These include the insulin, insulin receptor, glucose transporter, amylin and glucokinase genes. Molecular techniques have permitted rapid screening of these genes in NIDDM patients and controls. There is now a rather contradictory genetic literature for NIDDM, with weak disease associations reported and refuted for most candidate genes. However, pedigree analyses and DNA sequencing of available candidate genes and their regulatory regions have failed to implicate any of these in the common form of diabetes, NIDDM. Methodical application of random clones in well-defined NIDDM families may be the strategy of choice in finding the NIDDM genes, given the wide range of genes potentially involved in the glucose and lipoprotein metabolic disturbances seen in NIDDM.
家族研究表明，非胰岛素依赖型糖尿病（NIDDM）的病因中有很强的遗传因素，有证据表明存在一个具有共显性或显性效应的主要基因。可能存在基因剂量效应，即携带两个易感基因的人比携带一个易感基因的人患糖尿病的时间更早。对糖尿病基因的研究已导致许多参与控制葡萄糖稳态的基因被克隆和鉴定。这些基因包括胰岛素、胰岛素受体、葡萄糖转运蛋白、胰淀素和葡萄糖激酶基因。分子技术已能对NIDDM患者和对照者进行这些基因的快速筛查。目前关于NIDDM的遗传文献相当矛盾，大多数候选基因与疾病的关联报道都被否定。然而，对现有候选基因及其调控区域的系谱分析和DNA测序未能将这些基因中的任何一个与糖尿病的常见类型NIDDM联系起来。鉴于NIDDM中葡萄糖和脂蛋白代谢紊乱可能涉及广泛的基因，在明确界定的NIDDM家族中有条不紊地应用随机克隆可能是寻找NIDDM基因的首选策略。
