Detection of the placental epigenetic signature of the maspin gene in maternal plasma
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摘要The discovery of fetal DNA in the plasma of pregnant women has opened up new approaches for noninvasive prenatal diagnosis and monitoring. Up to now, the lack of a fetal DNA marker that can be universally detected in maternal plasma has limited the clinical application of this technology. We hypothesized that epigenetic differences between the placenta and maternal blood cells could be used for developing such a marker. By using bisulfite DNA sequencing, the methylation status of the maspin gene promoter in placental tissues and paired maternal blood cells from pregnant women was analyzed. The maspin gene promoter was found to be hypomethylated in placental tissues and densely methylated in maternal blood cells. Genotyping of a single nucleotide polymorphism within the unmethylated maspin sequences in maternal plasma demonstrated that these sequences were derived from the fetus. By using real-time quantitative methylation-specific PCR, unmethylated maspin sequences were detected in maternal plasma in all three trimesters of pregnancy and were cleared within 24 h after delivery. The maternal plasma concentration of unmethylated maspin sequences was elevated by a median of 5.7 times in preeclamptic pregnancies compared with nonpreeclamptic pregnancies. Hypomethylated maspin DNA is the first universal marker for fetal DNA in maternal plasma, thus allowing the measurement of fetal DNA concentrations in pregnancy-associated disorders, irrespective of fetal gender and genetic polymorphisms. Differential DNA methylation between the placenta and maternal blood cells may be exploited to develop further markers for noninvasive prenatal assessment.
著者Chim SSC, Tong YK, Chiu RWK, Lau TK, Leung TN, Chan LYS, Oudejans CBM, Ding CM, Lo YMD
期刊名稱Proceedings of the National Academy of Sciences
詳細描述To ORKTS: CHIM Siu Chung Stephen, TONG Yu Kwan, CHIU Wai Kwun Rossa contributed equally to this work.
出版年份2005
月份10
日期11
卷號102
期次41
出版社NATL ACAD SCIENCES
頁次14753 - 14758
國際標準期刊號0027-8424
語言英式英語
關鍵詞circulating nucleic acids; DNA methylation; noninvasive prenatal diagnosis
Web of Science 學科類別Multidisciplinary Sciences; MULTIDISCIPLINARY SCIENCES; Science & Technology - Other Topics

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