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线粒体 DNA 拷贝数与心血管疾病的关联:基于系统评价和荟萃分析的现有证据。

Association between mitochondrial DNA copy number and cardiovascular disease: Current evidence based on a systematic review and meta-analysis.

机构信息

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

Ministry of Education Key Laboratory of Women and Children's Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

PLoS One. 2018 Nov 7;13(11):e0206003. doi: 10.1371/journal.pone.0206003. eCollection 2018.

Abstract

BACKGROUND

Mitochondria are energy-producing structure of the cell and help to maintain redox environment. In cardiovascular disease, the number of mitochondrial DNA (mtDNA) will changes accordingly compare to normal condition. Some investigators ask whether it has a clear association between mtDNA and cardiovascular disease with its adverse events. Thus, we conduct the meta-analysis to assess the role of circulating mtDNA in evaluating cardiovascular disease.

METHODS

The meta-analysis was conducted in accordance with a predetermined protocol following the recommendations of Cochrane Handbook of Systematic Reviews. We searched the Pubmed, Embase, the Cochrane Central Register of Controlled Trials and World Health Organization clinical trials registry center to identify relevant studies up to the end of October 2017. Data were analyzed using STATA. Besides, publication bias and meta-regression analysis were also conducted.

RESULTS

We collected results from 5 articles for further analyses with 8,252 cases and 20,904 control. The normalized mtDNA copy number level is lower in cardiovascular disease (CVD) than the control groups with a pooled standard mean difference (SMD) of -0.36(95%CI,-0.65 to -0.08); The pooled odds ratio (OR) for CVD proportion associated with a 1-SD (standard deviation) decrease in mtDNA copy number level is 1.23 (95% CI,1.06-1.42); The OR for CVD patients with mtDNA copy number lower than median level is 1.88(95% CI,1.65-2.13); The OR for CVD patients with mtDNA copy number located in the lowest quartile part is 2.15(95% CI, 1.46-3.18); the OR between mtDNA copy number and the risk of sudden cardiac death (SCD) is 1.83(95% CI, 1.22-2.74).

CONCLUSION

Although inter-study variability, the overall performance test of mtDNA for evaluating CVD and SCD revealed that the mtDNA copy number presented the potential to be a biomarker for CVD and SCD prediction. Given that, the fewer copies of mtDNA, the higher the risk of CVD.

摘要

背景

线粒体是细胞的能量产生结构,有助于维持氧化还原环境。在心血管疾病中,与正常情况相比,线粒体 DNA(mtDNA)的数量会发生相应变化。一些研究人员询问 mtDNA 与心血管疾病及其不良事件之间是否存在明确的关联。因此,我们进行了荟萃分析,以评估循环 mtDNA 在评估心血管疾病中的作用。

方法

该荟萃分析按照预先制定的方案进行,遵循 Cochrane 系统评价手册的建议。我们在 Pubmed、Embase、Cochrane 中心对照试验注册库和世界卫生组织临床试验注册中心检索相关研究,截至 2017 年 10 月底。使用 STATA 进行数据分析。此外,还进行了发表偏倚和荟萃回归分析。

结果

我们从 5 篇文章中收集了进一步分析的结果,共有 8252 例病例和 20904 例对照。心血管疾病(CVD)患者的标准化 mtDNA 拷贝数水平低于对照组,合并标准均数差(SMD)为-0.36(95%CI,-0.65 至-0.08);与 mtDNA 拷贝数降低 1-SD(标准差)相关的 CVD 比例的合并优势比(OR)为 1.23(95%CI,1.06-1.42);mtDNA 拷贝数低于中位数水平的 CVD 患者的 OR 为 1.88(95%CI,1.65-2.13);mtDNA 拷贝数位于最低四分位部分的 CVD 患者的 OR 为 2.15(95%CI,1.46-3.18);mtDNA 拷贝数与心脏性猝死(SCD)风险之间的 OR 为 1.83(95%CI,1.22-2.74)。

结论

尽管存在研究间变异性,但 mtDNA 评估 CVD 和 SCD 的总体性能测试表明,mtDNA 拷贝数具有成为 CVD 和 SCD 预测的生物标志物的潜力。鉴于此,mtDNA 拷贝数越低,CVD 的风险越高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/add6/6221293/eb86d3d83276/pone.0206003.g001.jpg

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