围产期母婴端粒长度和线粒体 DNA 拷贝数与子痫前期的关系：一项前瞻性病例对照研究。
Association between the peripartum maternal and fetal telomere lengths and mitochondrial DNA copy numbers and preeclampsia: a prospective case-control study.
机构信息
Department of Obstetrics & Gynecology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China.
Department of Obstetrics & Gynecology, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, 210008, China.
出版信息
BMC Pregnancy Childbirth. 2022 Jun 13;22(1):483. doi: 10.1186/s12884-022-04801-0.
PURPOSE
To explore changes in telomere length (TL) and mitochondrial copy number (mtDNA-CN) in preeclampsia (PE) and to evaluate the combined effect of maternal TL and mtDNA-CN on PE risk.
METHODS
A case-control study of 471 subjects (130 PE cases and 341 age frequency matched controls with gestational age rank from 24 to 42 weeks) was conducted in Nanjing Drum Tower Hospital, Jiangsu Province of China. Relative telomere length (RTL) and mtDNA-CN were measured using quantitative polymerase chain reaction (qPCR), and PE risk was compared between groups by logistic regression analyses.
RESULTS
PE patients displayed longer RTL (0.48 versus 0.30) and higher mtDNA-CN (3.02 versus 2.00) in maternal blood as well as longer RTL (0.61 versus 0.35) but lower mtDNA-CN (1.69 versus 5.49) in cord blood (all p < 0.001). Exercise during pregnancy exerted an obvious effect of maternal telomere length prolongation. Multiparous women with folic acid intake during early pregnancy and those who delivered vaginally showed longer telomere length, while those factors imposed no or opposite effect on RTL in PE cases. Furthermore, RTL and mtDNA-CN were positively correlated in controls (in maternal blood r = 0.18, p < 0.01; in cord blood r = 0.19, p < 0.001), but this correlation was disrupted in PE patients in both maternal blood and cord blood. Longer maternal RTL and higher mtDNA-CN were associated with a higher risk of PE, and the ROC curve of RTL and mtDNA-CN for predicting PE risk presented an AUC of 0.755 (95% CI: 0.698-0.812).
CONCLUSIONS
The interaction of TL and mtDNA-CN may play an important role in the pathogenesis of PE and could be a potential biomarker of PE risk.
目的
探讨子痫前期（PE）患者端粒长度（TL）和线粒体 DNA 拷贝数（mtDNA-CN）的变化，并评估母体 TL 和 mtDNA-CN 联合对 PE 风险的影响。
方法
采用病例对照研究，纳入江苏省南京市鼓楼医院的 471 例受试者（130 例 PE 病例和 341 例胎龄 24 至 42 周的年龄频数匹配对照）。采用实时定量聚合酶链反应（qPCR）检测相对端粒长度（RTL）和 mtDNA-CN，采用逻辑回归分析比较各组间的 PE 风险。
结果
PE 患者的母血 RTL（0.48 比 0.30）和 mtDNA-CN（3.02 比 2.00）较长，脐血 RTL（0.61 比 0.35）较长而 mtDNA-CN（1.69 比 5.49）较低（均 P<0.001）。孕期运动对母体端粒长度延长有明显作用。早孕期补充叶酸且阴道分娩的经产妇端粒长度较长，而这些因素对 PE 患者的 RTL 无影响或产生相反的影响。此外，对照组母血和脐血中 RTL 与 mtDNA-CN 呈正相关（母血 r=0.18，P<0.01；脐血 r=0.19，P<0.001），但在 PE 患者中这种相关性在母血和脐血中均被破坏。较长的母血 RTL 和较高的 mtDNA-CN 与 PE 风险增加相关，RTL 和 mtDNA-CN 预测 PE 风险的 ROC 曲线 AUC 为 0.755（95%CI：0.698-0.812）。
结论
TL 和 mtDNA-CN 的相互作用可能在 PE 的发病机制中起重要作用，可能是 PE 风险的潜在生物标志物。
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