再生障碍性贫血线粒体突变与端粒长度相关性的研究

目的：研究再生障碍性贫血患者线粒体突变及端粒长度情况,了解两者间的相关性。方法选择2010~2014年确诊为再生障碍性贫血的患者45例,留取骨髓及口腔黏膜上皮标本以进行线粒体DNA ( mitochondrial DNA, mtDNA)突变和端粒长度的检测。线粒体全测序检测到了151个突变,分布在18个基因中,其中包括了40个沉默突变及28个框移突变。同时使用HBG作为内参基因,检测了再障患者和健康志愿者端粒的相对长度( relative T/S value,端粒长度)。结果分析发现非沉默突变的mtDNA突变与白细胞数、血红蛋白水平及血小板数成负相关。端粒长度与白细胞数、血红蛋白水平及血小板数成正相关性,而且非沉默突变的mtDNA突变与端粒长度呈负相关性。结论研究提示突变导致线粒体氧化呼吸链功能紊乱及端粒的缩短是再障患者骨髓衰竭病程中的一个重要因素,而且这两者还会互相影响。

Association of Mitochondrial DNA Mutation with Telomere Length in Patients with Aplastic Anemia

Objective To examine the association of mitochondrial DNA ( mtDNA) mutations with telomere length in patients with aplastic anemia ( AA) . Methods Bone marrow and oral epi-thelial samples were collected from 45 patients diagnosed as having AA between 2010-2014 for de-tection of mtDNA mutation and telomere length. Complete sequence analysis of mtDNA revealed 151 mutations in 18 genes, including 40 silent mutations and 28 frameshift mutations. Moreover, the relative length of telomere ( relative T/S value) was detected in AA patients and healthy volunteers, with HBG as internal control gene. Results Non-silent mutation of mtDNA was negatively correla-ted with the WBC count, hemoglobin level and platelet count. Relative T/S value was positively correlated with the WBC count, hemoglobin level and platelet count, and a negative correlation was found between the non-silent mutation of mtDNA and relative T/S value. Conclusion Mutation-caused functional impairment of the mitochondrial respiratory chain and telomere length shortening may play important roles in the process of hematopoietic failure in AA patients. Additionally, mtD-NA mutations and telomere length shortening influence each other.