线粒体tRNA^(Leu(UUR))基因点突变与1型糖尿病

Point mutation of mitochondrial tRNA Leu(UUR) gene and type 1 diabetes mellitus

目的 线粒体ｔ Ｒ Ｎ Ａ Ｌｅｕ（ Ｕ Ｕ Ｒ） 基因３２４３ 位点 Ａ→ Ｇ 突变是糖尿病的致病基因之一。本研究是为了了解该基因的突变在中国１ 型糖尿病患者中的情况以及与自身免疫导致１ 型糖尿病有无关联。方法 对１１６ 例随机收集的１ 型糖尿病患者用聚合酶链反应限制性内切酶消化作该点突变的筛选；８２ 例患者同时进行了谷氨酸脱羧酶（ Ｇ Ａ Ｄ） 抗体的测定。结果 发现１ 例该点突变（０ ．８６ ％ ） ，４８ 例 Ｇ Ａ Ｄ 抗体阳性（５８ ．５ ％ ） 。线粒体ｔ Ｒ Ｎ Ａ Ｌｅｕ（ Ｕ Ｕ Ｒ） 基因突变携带者 Ｇ Ａ Ｄ 抗体阴性，其家系成员糖尿病有不同的发病方式，但均表现为胰岛素缺乏。结论 线粒体ｔ Ｒ Ｎ Ａ Ｌｅｕ（ Ｕ Ｕ Ｒ） 基因异常所致糖尿病表现为胰岛素缺乏可能与自身免疫胰岛炎无关，而是一种独特的糖尿病亚型。

Objective Mitochondrial tRNA Leu(UUR) gene nt3243 A→G point mutation is one of the diabetic genes. This study aims to know the prevalence of the mutation in type 1 diabetes mellitus and whether serum autoimmune insulitis marker coexits with the mutation. Methods The mutation had been screened from 116 unrelated patients with type 1 diabetes mellitus by ApaI digestion of product of polymerase chain reaction amplification. Glutamic acid decarboxylase (GAD) antibody was detected in 82 cases. Results 1 case had the mutation (0.86%) but negative GAD antibody. None of the 48 patients with positive GAD antibody and none of the 41 patients with slowly progressive type 1 diabetes mellitus had the mutation. The diabetic family members demonstrated different onset types but shared the characteristic of insulin defficiency. Conclusion Our limited data suggested that diabetes mellitus caused by mitochondrial tRNA Leu(UUR) nt3243 A→G mutation was a distinct subtype and the phenotype of insulin dependent (or requiring) might not relate with autoimmune pancreatic isletis.