Heteroplasmy Level of the Mitochondrial tRNA^(Leu(UUR)) A3243G Mutation in a Chinese Family Is Positively Associated with Earlier Age-of-onset and Increasing Severity of Diabetes  

作　　者：Shi Zhang An-li Tong Yun Zhang Min Nie Yu-xiu Li Heng Wang 

机构地区：[1]Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health,Peking Union Medical College Hospital, Chinese Academy of Medical Sciences ＆ Peking Union Medical College, Beijing 100730, China

出　　处：《Chinese Medical Sciences Journal》2009年第1期20-25,共6页中国医学科学杂志（英文版）

摘　　要：Objective To investigate the mutations of mitochondrial genome in a pedigree with suspected maternally inherited diabetes and deafness and to explore the correlations between the mutations and clinical features. Methods Genomic DNA was isolated from blood leucocytes of each member of the pedigree. The mitochondrial genome was amplified with 24-pair primers that could cover the entire mitochondrial DNA. Direct sequencing of PCR products was used to identify any mitochondrial DNA mutations. Results Family members on the maternal side all harbored the tRNA^Lcu（UUR） A3243G mutation. The paternal side family members did not have the mutation. The age-of-onset of diabetes of the 4 maternal side family members was 15, 41, 44, and 65 years old, and their corresponding heteroplasmy level of the mutation was 34.5%, 14.9%, 14.6%, and 5.9%, respectively. The age-of-onset of diabetes and heteroplasmy level of A3243G mutation were negatively correlated with a correlation coefficient of -0.980（P=0.02）. Meanwhile, patient with high heteroplasmy level of A3243G mutation had relatively low severity of disease. Moreover, 6 reported polymorphisms and 2 new variants were found. Conclusions The main cause of diabetes in this pedigree is the tRNA^Lcu（UUR） A3243G mutation. However, other gene variants may contribute to its pathogenicity. The heteroplasmy level of the tRNA^Lcu（UUR） A3243G mutation is positively associated with earlier age-of-onset and increasing severity of diabetes.

关 键 词：maternally inherited diabetes and deafness tRNA^Lcu（UUR） A3243G mutation beteroplasmy 

分 类 号：R587.104[医药卫生—内分泌] R596[医药卫生—内科学]