妊娠早、中期游离 DNA 与血清标志物的相关性研究。

Relationships between cell-free DNA and serum analytes in the first and second trimesters of pregnancy.

机构信息

From the Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, Massachusetts; the Division of Genetics, Department of Pediatrics, Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts; the Department of Pathology and Laboratory Medicine, Women and Infants Hospital and the Alpert School of Medicine at Brown University, Providence, Rhode Island; the Institute of Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, Massachusetts; and the Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York.

出版信息

Obstet Gynecol. 2010 Sep;116(3):673-678. doi: 10.1097/AOG.0b013e3181ea2dd1.

DOI:10.1097/AOG.0b013e3181ea2dd1

PMID:20733451

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2975594/

Abstract

OBJECTIVE

To assess the relationship between first- and second-trimester cell-free DNA levels and maternal serum screening markers.

METHODS

First- and second-trimester residual maternal serum samples from 50 women were obtained. First-trimester (pregnancy-associated plasma protein A and beta-hCG) and second-trimester serum analytes (beta-hCG, alpha-fetoprotein, unconjugated estriol, and inhibin A) had been measured at the time of sample receipt. All fetuses were male as confirmed by birth records. Cell-free DNA was extracted and measured by real-time quantitative polymerase chain reaction amplification using glyceraldehyde phosphate dehydrogenase and DYS1 as markers of total DNA and fetal DNA, respectively. Determination of linear associations between first- and second-trimester serum markers and cell-free DNA levels using Pearson correlations was performed.

RESULTS

Statistically significant correlations between first-trimester pregnancy-associated plasma protein A multiples of the median and both total (r=0.36, P=.016) and fetal (r=0.41, P=.006) DNA in the first trimester were observed. There were no significant correlations between first-trimester serum human chorionic gonadotropin or any second-trimester serum marker with DNA levels.

CONCLUSION

Correlation between serum pregnancy-associated plasma protein A and first-trimester circulating cell-free fetal and total DNA levels is a novel finding. Pregnancy-associated plasma protein A is a glycoprotein of placental origin, and its correlation to cell-free fetal DNA in maternal serum suggests a common tissue origin through apoptosis of placental cells. However, because pregnancy-associated plasma protein A and cell-free DNA were only marginally correlated and cell-free DNA can be reliably detected in the first trimester, the addition of cell-free DNA to serum screening strategies may be helpful in predicting adverse pregnancy outcome.

LEVEL OF EVIDENCE

II.

摘要

目的

评估早、中孕期游离 DNA 水平与母血清筛查标志物之间的关系。

方法

收集 50 例女性的早、中孕期剩余母血清样本。在收到样本时，已检测了早孕期（妊娠相关血浆蛋白 A 和β-HCG）和中孕期血清分析物（β-HCG、甲胎蛋白、未结合雌三醇和抑制素 A）。所有胎儿均为男性，这是通过出生记录确认的。通过实时定量聚合酶链反应扩增，使用甘油醛磷酸脱氢酶和 DYS1 分别作为总 DNA 和胎儿 DNA 的标志物，提取并测量游离 DNA。使用 Pearson 相关性分析确定早、中孕期血清标志物与游离 DNA 水平之间的线性关联。

结果

早孕期妊娠相关血浆蛋白 A 倍数与总 DNA（r=0.36，P=.016）和胎儿 DNA（r=0.41，P=.006）在早孕期均存在显著相关性。早孕期血清人绒毛膜促性腺激素或任何中孕期血清标志物与 DNA 水平之间均无显著相关性。

结论

血清妊娠相关血浆蛋白 A 与早孕期循环游离胎儿和总 DNA 水平之间的相关性是一个新发现。妊娠相关血浆蛋白 A 是胎盘来源的糖蛋白，其与母血清中游离胎儿 DNA 的相关性提示共同的组织起源，即胎盘细胞凋亡。然而，由于妊娠相关血浆蛋白 A 和游离 DNA 仅呈边缘相关，且游离 DNA 可在早孕期可靠检测到，因此将游离 DNA 加入血清筛查策略可能有助于预测不良妊娠结局。