线粒体基因突变糖尿病的临床基因诊断技术

Clinical Genetic Diagnostic Technique for Mitochondrial Gene Mutation in Patients with Type 2 Diabetes

目的 :了解线粒体基因突变在我国2型糖尿病 (DM)人群中的存在情况 ,并为建立一种简便、快速的线粒体基因突变糖尿病的诊断方法提供基础。方法 :采用PCR -RFLP方法对随机抽取的无亲缘关系的178例2型DM患者和150例健康对照的线粒体DNA突变热点区域tRNALeu(UUR)基因及其邻近区域内(nt2995～3494)4个位点 ,即nt3243、3316、3394、3426进行突变筛查。结果 :在178例2型DM患者中发现5例nt3316G→A突变 ;对照组中未检出任何突变(P<0.05)。nt3316G→A突变频率为2 81% ,突变使非极性的丙氨酸被极性的苏氨酸所取代 (GCC→ACC)。结论 :nt3316G→A突变可能是2型糖尿病的易感因素之一。该方法简便易行 ,具有较高的特异性和敏感性 。

Objective:To develop a clinical genetic diagnostic technique for mitochondr ial gene mutation in patients with type 2 diabetes mellitus(DM).Methods:Four pos itions(nt3 243,3 316,3 394 and 3 426)were screened in 178 randomly selected and unrelated patients with type 2 DM(group I) and 150 normal controls(group II) by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).R esults:Five patients with the mutation of mtDNA nt3 316 G→A were identified in group I and no mutation was detected in group II(P<0.05).The prevalence of nt3 3 16 G→A mutation was 2.81%.This mutation changed a nonpolar alanine into a pola r threonine(GCC→ACC).Conclusion:The point mutation at nt3 316 G→A may confer a higher susceptibility upon type 2 DM.This diagnostic technique is a high specia l,high sensitive and time-saving method,which can be performed in clinical diag nosis and colonial screening.