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孕妇白细胞端粒长度与线粒体DNA拷贝数之间的关联:一项初步研究。

The association between leukocyte telomere length and mitochondrial DNA copy number in pregnant women: a pilot study.

作者信息

Qiu Chunfang, Enquobahrie Daniel A, Gelaye Bizu, Hevner Karin, Williams Michelle A

出版信息

Clin Lab. 2015;61(3-4):363-9. doi: 10.7754/clin.lab.2014.140313.

Abstract

BACKGROUND

Both short telomere length and mitochondrial dysfunction have been associated with pregnancy complications, such as preeclampsia and intrauterine growth restriction. However, the relationship between these two biomarkers of oxidative stress, during pregnancy, is unknown. This study investigated the association of leukocyte telomere length with mitochondrial DNA (mtDNA) copy number, an indicator of mitochondrial density and possible mitochondrial dysfunction, using maternal blood samples collected from women with pregnancies uncomplicated by gestational diabetes or hypertensive disorders.

METHODS

Leukocyte telomere length and mtDNA copy number were determined in 75 pregnant women using quantitative real-time quantitative PCR. Bivariate and multivariable linear regression procedures were used to evaluate associations of these two biomarkers.

RESULTS

Leukocyte mtDNA copy number (natural-logarithm) was positively associated with telomere length (Pearson correlation coefficient = 0.30, p-value = 0.009). After adjusting for maternal age and plasma vitamin B12, natural-log mtDNA copy number increased by 0.80 (f = 0.80; 95% CI 0.25 - 1.34, p-value = 0.005) for every 1 unit increase of telomere length. Approximately 11% of the variation in natural-long mtDNA copy number was explained by the model (adjusted R2 = 0.11).

CONCLUSIONS

This cross sectional data suggests an association of mtDNA copy number with telomere length, two emergent biological markers of potential importance in perinatal health research. The consequences of oxidative stress, cellular senescence (as reflected by relatively shorter telomere length) and mitochondrial dysfunction, on the course and outcomes of pregnancy remain to be elucidated in larger prospective studies that include these biological markers.

摘要

背景

端粒长度缩短和线粒体功能障碍均与妊娠并发症有关,如先兆子痫和胎儿生长受限。然而,这两种氧化应激生物标志物在孕期的关系尚不清楚。本研究使用从无妊娠糖尿病或高血压疾病并发症的孕妇采集的母血样本,调查白细胞端粒长度与线粒体DNA(mtDNA)拷贝数之间的关联,线粒体DNA拷贝数是线粒体密度和可能的线粒体功能障碍的指标。

方法

采用定量实时定量PCR测定75名孕妇的白细胞端粒长度和mtDNA拷贝数。使用双变量和多变量线性回归程序评估这两种生物标志物的关联。

结果

白细胞mtDNA拷贝数(自然对数)与端粒长度呈正相关(Pearson相关系数=0.30,p值=0.009)。在调整孕妇年龄和血浆维生素B12后,端粒长度每增加1个单位,自然对数mtDNA拷贝数增加0.80(f=0.80;95%CI 0.25-1.34,p值=0.005)。该模型解释了自然对数mtDNA拷贝数约11%的变异(调整后R2=0.11)。

结论

该横断面数据表明mtDNA拷贝数与端粒长度有关,这是围产期健康研究中两个具有潜在重要性的新兴生物标志物。氧化应激、细胞衰老(以相对较短的端粒长度反映)和线粒体功能障碍对妊娠过程和结局的影响,仍有待在纳入这些生物标志物的更大规模前瞻性研究中阐明。

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