Hypermethylated ERG as a cell-free fetal DNA biomarker for non-invasive prenatal testing of Down syndrome.
BACKGROUND
Previous reports have shown that the ERG gene is hypermethylated in the placenta and hypomethylated in maternal blood cells. In this study, we explore the feasibility of hypermethylated ERG as a cell-free fetal (cff) DNA biomarker for non-invasive prenatal testing (NIPT) of Down syndrome.


METHODS
We randomly selected 90 healthy pregnant women, including 30 cases at each trimester of pregnancy. In addition, 15 pregnant women were recruited as the case group whose fetuses had been confirmed to have trisomy 21 by amniotic fluid analysis at 18th to 26th week gestation. Using HpaII, MspІ to digest cell-free maternal plasma DNA, we performed SYBR Green PCR to detect methylated sites of ERG sequences, and analyzed the concentrations of cff DNA in maternal plasma in different gestational trimesters and the case group.


RESULTS
The ERG median concentrations of the maternal plasma after Hpa II digestion (LG copies/ml) in first, second and third-trimesters were 5.38, 6.10, and 7.04, respectively (Kruskal-Wallis, P<0.01); and that in the trisomy 21 case group was 6.85, which was higher than the second-trimester (Mann-Whitney, P<0.01).


CONCLUSIONS
The study demonstrated that ERG gene is hypermethylated in cff DNA but hypomethylated in maternal DNA; and the median concentration of ERG gene in the trisomy 21 case group is higher than that in the gestational trimester matched normal group. ERG gene, as a fetal DNA biomarker, may be useful for NIPT of Down syndrome.
Department of Center Laboratory, Baoan Maternal and Child Health Hospital, Shenzhen, China.
Xi
X
Chen
Department of Center Laboratory, Baoan Maternal and Child Health Hospital, Shenzhen, China. Electronic address: xionglk@sina.cn.
Likuan
L
Xiong
Department of Center Laboratory, Baoan Maternal and Child Health Hospital, Shenzhen, China.
Ting
T
Zeng
Department of Center Laboratory, Baoan Maternal and Child Health Hospital, Shenzhen, China.
Kelin
K
Xiao
Department of Center Laboratory, Baoan Maternal and Child Health Hospital, Shenzhen, China.
Yanping
Y
Huang
Department of Prenatal Diagnosis Center, 2(nd) Clinical Medical College of Jinan University, Shenzhen, China.
Hui
H
Guo
Department of Prenatal Diagnosis Center, 2(nd) Clinical Medical College of Jinan University, Shenzhen, China.
Jinghui
J
Ren
D004247:DNA / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics*; D004314:Down Syndrome / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D011247:Pregnancy; D011296:Prenatal Diagnosis; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
C072312:ERG protein, human; D005819:Genetic Markers; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D004247:DNA
Cell-free fetal DNA; Down syndrome; Hypermethylated ERG; Non-invasive prenatal testing; SYBR Green PCR