家族性2型糖尿病线粒体基因突变发生率及其临床意义

The prevalence of mitochondrial gene mutation and its clinical significance in familial type 2 diabetes mellitus in Nanchang

目的探讨家族性2型糖尿病(T2DM)线粒体基因tRNA^(Leu(UUR))mt3243A→G突变发生率及突变家系成员病情演变与临床特征。方法采用PCR/ApaI酶切法对66个家族性T2DM的家系成员共计518人进行突变筛查,并随访3年,观察其临床特点及胰岛β细胞功能变化。结果共发现突变阳性12例,其中3例为已确诊的T2DM患者,1例为糖耐量减低(IGT)患者,8例为糖耐量正常(NGT)者。随访3年后突变阳性者的耳聋症状加重,BMI、HOMA-IR下降,部分成员出现了白蛋白尿,2例演变为DM,3例进展为IGT,其中一例突变阳性者新生一女也为该基因突变阳性。结论家族性T2DM患者中线粒体基因突变发生率约为2.7%,且突变患者的临床表现呈一定的异质性;线粒体基因突变阳性的NGT者是糖尿病高危人群,易演变为IGT或DM,而IGT者易进展为DM。

Objective To study the prevalence of mitochondrial tRNA^Leu（UUR）mt3243A→G mutations and its clinical significance in familial type 2 diabetes（T2DM） in Nanchang. Methods 518 cases of T2DM in 66 parentage were selected. The mutation was assayed by PCR-restriction fragment length polymorphism technique. The positive family were followed up for three years. Results Three people had T2DM in 12 positive patients;one,impaired glucose tolerance（IGT）;other eigth people, normal glucose tolerance （NGT）. People with the mutation after three years follow-up showed an aggravated hearing impairment,decreased BMI and HOMA-IR, and abnormal albuminuria, and diabetes （n = 2） and IGT （n--3） occurred in people with mutation. A neonate of a subject with the mitochondrial mutation showed the same mutation as her mother. Conclusions The prevalence of the mitochondrial tRNA^Leu（UUR） mt3243A→G mutation is 2.7% in T2DM patients in nanchang. The clinical phenotype of these patients with mutations is heterogeneous. The people with mutation are at high risk for becoming IGT from NGT, and DM from IGT.