Complete sequence analysis of mitochondrial DNA and telomere length in aplastic anemia
Complete sequence analysis of mitochondrial DNA and telomere length in aplastic anemia
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再生障碍性贫血线粒体 DNA 和端粒长度的完整序列分析
DOI：
10.3892/ijmm.2014.1898
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发表时间：
2014-11-01
影响因子：
5.4
通讯作者：
Jing, Jingyan
中科院分区：
文献类型：
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作者：
Cui, Xing;Wang, Junqiang;Jing, Jingyan
本研究主要是为了检验线粒体 DNA (mtDNA) 突变和端粒长度可能与再生障碍性贫血 (AA) 相关的假设。我们的研究对 2010 年至 2013 年间在山东中医药大学附属医院首次诊断的 40 名 AA 患者进行了单机构分析。采集 AA 患者 (n=40) 的骨髓和口腔上皮样本，用于 mtDNA 突变和端粒长度测定。采集 40 名健康志愿者的骨髓标本作为端粒长度检查的对照。通过聚合酶链式反应（PCR）扩增线粒体基因组，产物用于测序和分析。我们在 40 名 AA 患者的 18 个基因中检测到 146 个异质突变，其中包括 39 个沉默突变和 28 个移码突变。我们使用γ珠蛋白基因（HBG）作为实时PCR中的对照基因来调查AA患者和健康志愿者的相对端粒长度测量值。端粒长度表示为相对 T/S 值。我们观察到 mtDNA 非沉默突变与白细胞 (WBC) 计数、血红蛋白和血小板计数之间呈负相关。值得注意的是，相对T/S值与WBC计数、血红蛋白和血小板计数呈正相关，非沉默突变与相对T/S值呈负相关。我们的结论是，突变和端粒长度缩短引起的线粒体呼吸链功能损伤可能在AA患者的造血衰竭过程中发挥重要作用。此外，线粒体DNA突变和端粒长度缩短相互影响。
The present study was primarily undertaken to examine the hypothesis that mitochondrial DNA (mtDNA) mutations and telomere length may be associated with aplastic anemia (AA). Our study included a single institution analysis of 40 patients presenting with AA first diagnosed at the Affiliated Hospital of Shandong, University of Traditional Chinese Medicine between 2010 and 2013. Bone marrow and oral epithelial samples were collected from patients with AA (n=40) for mtDNA mutation and telomere length determinations. Bone marrow specimens were collected from 40 healthy volunteers as controls for the examination of telomere length. The mitochondrial genome was amplified by polymerase chain reaction (PCR), and the products were used for sequencing and analysis. We detected 146 heteroplasmic mutations in 18 genes from 40 patients with AA, including 39 silent mutations and 28 frameshift mutations. We used the gamma globin gene (HBG) as the control gene in real-time PCR to survey the relative telomere length measurements of the patients with AA and the healthy volunteers. Telomere length was expressed as the relative T/S value. We observed a negative correlation between the mtDNA non-silent mutation and the white blood cell (WBC) count, hemoglobin and platelet count. Of note, there was a positive correlation between the relative T/S value and WBC count, hemoglobin and platelet count, and a negative correlation between the non-silent mutation and the relative T/S value. We conclude that the functional impairment of the mitochondrial respiratory chain induced by mutation and telomere length shortening may play an important role in the process of hematopoietic failure in patients with AA. Additionally, mtDNA mutations and telomere length shortening influenced each other.