Novel mitochondrial 16S rRNA mutation, 3200T→C, associated with adult-onset type 2 diabetes  

新发现的线粒体 1 6SrRNA基因突变 ,32 00T→C ,与成人期发作二型糖尿病相关(英文)

作　　者：杨涛[1,4] 林青云[1] 曾文和 汤瑞芬[1] 甘尔惠 陈婉珊[1] 潘妙娟[1] 巫向前[5] 彭智培[2] 

机构地区：[1]Department of Chemical Pathology,the Chinese University of Hong Kong,Hong Kong,China [2]Department of Ophthalmology&Visual Sciences,the Chinese University of Hong Kong,Hong Kong,China [3]Department of Medicine,United Christian Hospital,Hong Kong,China [4]Department of Medical Genetics,Institute of Basic Medieal Sciences,Chinese Acadelny of Medical Sciences&Peking Union Medieal College,Beijing 100005,China [5]Heahh School,Shanghai Second Medical University,Shanghai 2O0025,China

出　　处：《Chinese Medical Journal》2002年第5期753-758,共6页中华医学杂志（英文版）

基　　金：ThisstudywassupportedbyDirectGrantsfromtheChineseUniversityofHongKong (No 2 0 40 5 85and 2 0 40 661)

摘　　要：Objective To investigate the role of a potential diabetes related mitochondrial region, which includes two previously reported mutations, 3243AG and 3316GA, in Chinese patients with adult onset type 2 diabetes Methods A total of 277 patients and 241 normal subjects were recruited for the study Mitochondrial nt 3116-3353, which spans the 16S rRNA, tRNA leu(UUR) and the NADH dehydrogenase 1 gene, were detected using polymerase chain reaction (PCR), direct DNA sequencing, PCR restriction fragment length polymorphism and allele specific PCR Variants were analyzed by two tailed Fisher exact test The function of the variants in 16S rRNA were predicted for minimal free energy secondary structures by RNA folding software mfold version 3 Results Four homoplasmic nucleotide substitutions were observed, 3200TC, 3206CT, 3290TC and 3316GA Only the 3200TC mutation is present in the diabetic population and absent in the control population No statistically significant associations were found between the other three variants and type 2 diabetes The 3200TC and 3206CT nucleotide substitutions located in 16S rRNA are novel variants The 3200TC caused a great alteration in the minimal free energy secondary structure model while the 3206CT altered normal 16S rRNA structure little Conclusions The results suggest that the 3200TC mutation is linked to the development of type 2 diabetes, but that the other observed mutations are neutral In contrast to the Japanese studies, the 3316GA does not appear to be related to type 2 diabetes目的　两个线粒体突变 32 4 3A→G和 3316G→A已经被报道发现在糖尿病患者中 ,本研究旨在调查这个可能的糖尿病相关区域 3116→ 335 3在中国人二型糖尿病中的角色。方法　应用聚合酶链反应 ,直接的DNA测序 ,限制性长度片段多态性和等位特异聚合酶链反应等方法筛查 2 77个二型糖尿病患者和 2 4 1个正常对照的线粒体目的基因区域。对检出的序列改变进行Fisher精确统计分析 ,并应用RNA折叠软件mfold预测 16SrRNA基因区域的变异所引起的最小自由能二级结构改变以确定其功能意义。结果　检出 4个同质体碱基取代 :32 0 0T→C ,32 0 6C→T ,32 90T→Cand 3316G→A。其中 32 0 0T→C只出现在患者中 ,另外三个在患者和正常人中均有检出 ,统计分析显示其频率的不同无显著意义。 32 0 0T→C和 32 0 6C→T位于16SrRNA ,为该研究首次检出 ,前者引起了最小自由能二级结构模型的极大改变 ,而后者几乎没有引起结构变化。结论　本结果建议 32 0 0T→C与二型糖尿病的发展相关 ,而其他几种变异的影响是中性的。不同于日本人的研究 ,3316C→T与二型糖尿病无关。

关 键 词：type 2 diabetes  ·  mitochondrial  DNA · 16S ribosomal RNA  ·  RNA secondary structure modeling 

分 类 号：R587.1[医药卫生—内分泌]