Faculty of Medicine of Sfax, Human Molecular Genetic Laboratory, Sfax, Tunisia.
J Diabetes Complications. 2010 Jul-Aug;24(4):270-7. doi: 10.1016/j.jdiacomp.2009.11.002. Epub 2010 Jan 4.
Diabetes mellitus (DM) is a heterogeneous disorder characterized by the presence of chronic hyperglycemia. Genetic factors play an important role in the development of this disorder, and several studies reported mutations in nuclear genes implicated in the insulin function. Besides, DM can be maternally transmitted in some families, possibly due to the maternal mitochondrial inheritance. In fact, mitochondrial genes may be plausible causative agents for diabetes, since mitochondrial oxidative phosphorylation plays an important role in glucose-stimulated insulin secretion from beta cells.
In this report, we screened two Tunisian families with mitochondrial diabetes for the m.3243A>G and the m.14709T>C mutations, respectively, in the tRNA(Leu(UUR)) and the tRNA(Glu) genes.
The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the sequence-specific primers by polymerase chain reaction (SSP-PCR) analysis in the leucocytes and the buccal mucosa in the members of the two families showed the absence of the m.3243A>G mutation and the presence of the heteroplasmic m.14709T>C mutation in the tRNA(Glu) gene in the two tested tissues.
We conclude that the m.14709T>C mutation in the tRNA(Glu) gene could be a cause of mitochondrial diabetes in Tunisian affected families. In addition, the heteroplasmic loads correlated with the severity and the onset of mitochondrial diabetes in one family but not in the other, suggesting the presence of environmental factors or nuclear modifier genes.
糖尿病（DM）是一种以慢性高血糖为特征的异质性疾病。遗传因素在该疾病的发展中起着重要作用，几项研究报告了核基因中的突变，这些基因与胰岛素功能有关。此外，DM 可能在一些家族中呈母系遗传，可能是由于线粒体母系遗传。事实上，线粒体基因可能是糖尿病的合理致病因素，因为线粒体氧化磷酸化在β细胞的葡萄糖刺激胰岛素分泌中起着重要作用。
在本报告中，我们分别对两个有母系遗传糖尿病的突尼斯家族进行了 m.3243A>G 和 m.14709T>C 突变的筛查，这些突变分别位于 tRNA(Leu(UUR))和 tRNA(Glu)基因中。
对两个家族成员的白细胞和口腔黏膜进行聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和聚合酶链反应-序列特异性引物（SSP-PCR）分析显示，在两种检测组织中均未发现 m.3243A>G 突变，而存在 tRNA(Glu)基因中的异质 m.14709T>C 突变。
我们得出结论，tRNA(Glu)基因中的 m.14709T>C 突变可能是突尼斯受影响家族中母系遗传糖尿病的原因。此外，在一个家族中，异质负荷与线粒体糖尿病的严重程度和发病时间相关，但在另一个家族中则不相关，这表明存在环境因素或核修饰基因。
