Lack of association between mutations of gene-encoding mitochondrial D310 (displacement loop) mononucleotide repeat and oxidative stress in chronic dialysis patients in Taiwan.
Lack of association between mutations of gene-encoding mitochondrial D310 (displacement loop) mononucleotide repeat and oxidative stress in chronic dialysis patients in Taiwan.
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DOI：
10.1186/1477-5751-8-10
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发表时间：
2009-11-05
期刊：
影响因子：
--
通讯作者：
Tiao MM
中科院分区：
文献类型：
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作者：
Chen JB;Lin TK;Liao SC;Lee WC;Lee LC;Liou CW;Wang PW;Tiao MM
线粒体（mt）对活性氧（ROS）高度敏感。在这项研究中，我们研究了慢性透析患者中mtDNA中对ROS和氧化应激标记物高度敏感的置换环（D环）区域之间的关联。我们招募了184名慢性透析患者和213名年龄匹配的健康受试者进行比较。血液中的氧化应激标志物，如硫代巴比妥酸反应物质（TBARS）和游离巯基，和mtDNA拷贝数进行了测定。一种单核苷酸重复序列（CCCC），在线粒体DNA的303和316-318（D310）之间的核苷酸序列中发现了CCCTCCCC）。根据D310单核苷酸肽重复序列的改变，受试者被分为4个亚组：7-C、8-C、9或10-C和T至C转换。慢性透析患者的氧化应激水平较高，表现为TBARS和mtDNA拷贝数水平较高，游离巯基水平较低。透析和对照受试者中7-C、8-C和9- 10 C的分布如下：7-C（38% vs. 31.5%）、8-C（35.3% vs. 43.2%）和9- 10 C（24.5% vs. 22.1%）。尽管透析患者和对照受试者之间的TBARS水平、游离巯基和D310重复亚组中的mtDNA拷贝数（T到C转换除外）存在显著差异，但同一研究队列中的事后分析显示无显著差异。虽然慢性透析患者的氧化应激水平升高，并导致mtDNA拷贝数的代偿性增加，但mtDNA区域（D310）中对ROS敏感的同源C重复序列与这些患者的氧化应激标志物无关。
Mitochondria (mt) are highly susceptible to reactive oxygen species (ROS). In this study, we investigated the association between a region within the displacement loop (D-loop) in mtDNA that is highly susceptible to ROS and oxidative stress markers in chronic dialysis patients. We enrolled 184 chronic dialysis patients and 213 age-matched healthy subjects for comparison. Blood levels of oxidative stress markers, such as thiobarbituric acid reactive substances (TBARS) and free thiol, and the mtDNA copy number were determined. A mononucleotide repeat sequence (CCCC...CCCTCCCCCC) between nucleotides 303 and 316-318 (D310) was identified in mtDNA. Depending on alterations in the D310 mononucleotide repeat, subjects were categorized into 4 subgroups: 7-C, 8-C, 9 or 10-C, and T-to-C transition. Oxidative stress was higher in chronic dialysis patients, evidenced by higher levels of TBARS and mtDNA copy number, and a lower level of free thiol. The distribution of 7-C, 8-C, and 9-10C in dialysis and control subjects was as follows: 7-C (38% vs. 31.5%), 8-C (35.3% vs. 43.2%), and 9-10C (24.5% vs. 22.1%). Although there were significant differences in levels of TBARS, free thiol, and the mtDNA copy number in the D310 repeat subgroups (except T-to-C transition) between dialysis patients and control subjects, post hoc analyses within the same study cohort revealed no significant differences. Although oxidative stress was elevated in chronic dialysis patients and resulted in a compensatory increase in the mtDNA copy number, homopolymeric C repeats in the mtDNA region (D310), susceptible to ROS, were not associated with oxidative stress markers in these patients.