早发糖尿病患者线粒体DNA tRNA Leu(UUR)突变的研究

目的 探讨天津地区早发糖尿病(DM)患者线粒体DNA tRNA^leu(UUR) 3243A→G突变的发生率及其相关性。方法 随机选取无亲缘关系、发病年龄≤45岁的DM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，以聚合酶链反应、限制性内切酶片段长度多态性及克隆的方法检测线粒体基因tRNA^tLeu(UUR)3243A→G突变，并进行家系研究。结果 DM组发现2例3243A→G突变，检出率为0．6％，有家族史的DM患者中发生率为1．2％。对照组未发现此突变。3243A→G突变先证者呈典型的线粒体DM表现，其家庭成员的临床表型和基因突变异质性不一致。结论 tRNA^Leu(UUR)3243A→G突变在天津地区发病年龄≤45岁的DM患者中检出率低，在合并其他线粒体病的患者中发生率较高；该突变异质性比例在有丝分裂组织中可能随年龄增加而减小。

Study on the mtDNA tRNALeu(UUR) mutation in diabetics with onset age less than 45 years

Objective To investigate the prevalence of mtDNA A3243G mutation in the early onset diabetics in Tianjin for exploring the relationship between mtDNA mutation and diabetes. Methods 348 kinship-free diabetics whose ages at onset were less than 45y were randomly recruited, with 207 control subjects. The PCR-RFLP and cloning techniques were applied to screen the A to G substitution at nucleotide 3243 of mtDNA tRNA~(LEU(UUR)). Meanwhile, the clinical and genetic analysis was done from one pedigree. Results We detected two diabetics harboring the well-known a3243g mutation with the mutation frequency of 0.6%. While the mutation frequency in diabetics with (positive) family history was 1.2%, and zero in the control subject. The proband showed a typical (picture) of mitochondrial diabetes mellitus, while the other family members harboring the same (mutation) had heterogeneous presentation. Conclusion The prevalence of mtDNA A3243G mutation in early onset diabetes of Tianjin is low, but relatively higher in diabetes complicated with other (symptoms) of mitochondrial disease. Furthermore, its heterogeneity would decrease with aging in (mitotic) tissue.