早发糖尿病线粒体基因突变的研究

目的研究天津地区早发糖尿病(发病年龄≤45岁)中线粒体基因突变的发生率及其相关性。方法随机选取无血缘关系、发病年龄≤45岁的糖尿病患者348例;对照组207名,收集相应临床资料,提取外周血基因组DNA,应用聚合酶链反应-限制性片段长度多态性及克隆技术检测线粒体基因点突变。结果糖尿病组线粒体基因点突变总的发生率为8.3%,明显高于对照组(3.3%)(P<0.05),其中17例ND412026A→G突变(4.9%);10例ND1点突变(2.9%),其中包括4例3316G→A突变(1.2%),5例3394T→C突变(1.4%),1例3426A→G突变(0.3%);2例3243A→G突变,检出率为0.6%。在对照组中发现4例12026A→G(1.9%);2例3394T→C突变(0.9%);1例G3316G→A突变(0.5%);未发现3243A→G突变和3426A→G突变。结论天津地区早发糖尿病患者存在多种线粒体基因点突变。

Study on the mitochondrial DNA mutations in patients with early-onset diabetes mellitus

OBJECTIVE: To investigate the prevalence of mitochondrial DNA (mtDNA) mutations in patients with early-onset diabetes in Tianjin, and to explore the relationship between mtDNA mutations and diabetes. METHODS: 348 non-related patients whose age at onset of diabetes was less than 45 years were randomly recruited, and 207 non-related and non-diabetic subjects were enrolled as controls. All their clinical and biochemical data were collected. Total genome was extracted conventionally from the participants' peripheral leucocytes, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and cloning techniques were applied to the screening of mtDNA mutations (including the 3316, 3394 and 3426 in ND1 region, 12026 in ND4 region, and tRNA Leu(UUR)] 3243 A-->G mutation). RESULTS: The authors found 17 diabetics harboring the 12026 A-->G mutation in ND4 region (4.9%), 10 diabetics with mutations in ND1 region (including 5 diabetics with the 3394 T-->C mutation, 4 diabetics with 3316 G-->A mutation, one with 3426 A-->G mutation), and only two with the known 3243 A-->G mutation (0.6%). On the contrary, one control subject with the 3316 G-->A mutation, two with 3394 T-->C mutation and four with 12026 A-->G mutation were found. The prevalence of mtDNA mutations in the patient group is significantly higher than that in the control group (3.3%) (P<0.05). CONCLUSION: The above findings suggest that mtDNA mutation may be implicated in the pathogenesis of the examined diabetes.