Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, Korea.
PLoS One. 2013 Nov 1;8(11):e78136. doi: 10.1371/journal.pone.0078136. eCollection 2013.
Quantification of cell-free fetal DNA by methylation-based DNA discrimination has been used in non-invasive prenatal testing of fetal chromosomal aneuploidy. The maspin (Serpin peptidase inhibitor, clade B (ovalbumin), member 5; SERPINB5) gene, located on chromosome 18q21.33, is hypomethylated in the placenta and completely methylated in maternal blood cells. The objective of this study was to evaluate the accuracy of non-invasive detection of fetal trisomy 18 using the unmethylated-maspin (U-maspin) gene as a cell-free fetal DNA marker and the methylated-maspin (M-maspin) gene as a cell-free total DNA marker in the first trimester of pregnancy.
METHODOLOGY/PRINCIPAL FINDINGS: A nested case-control study was conducted using maternal plasma collected from 66 pregnant women, 11 carrying fetuses with trisomy 18 and 55 carrying normal fetuses. Median U-maspin concentrations were significantly elevated in women with trisomy 18 fetuses compared with controls (27.2 vs. 6.7 copies/mL; P<0.001). Median M-maspin concentrations were also significantly higher in women with trisomy 18 fetuses than in controls (96.9 vs. 19.5 copies/mL, P<0.001). The specificities of U-maspin and M-maspin concentrations for non-invasive fetal trisomy 18 detection were 96.4% and 74.5%, respectively, with a sensitivity of 90.9%.
Our results suggest that U-maspin and M-maspin concentrations may be useful as potential biomarkers for non-invasive detection of fetal trisomy 18 in the first trimester of pregnancy, irrespective of the sex and genetic variations of the fetus.
基于甲基化的 DNA 区分的游离胎儿 DNA 定量已用于胎儿染色体非整倍体的无创产前检测。位于 18q21.33 染色体上的 maspin（丝氨酸蛋白酶抑制剂，B 族（卵白蛋白），成员 5；SERPINB5）基因在胎盘组织中呈低甲基化，而在母体血细胞中完全甲基化。本研究的目的是评估使用未甲基化-maspin（U-maspin）基因作为游离胎儿 DNA 标志物和甲基化-maspin（M-maspin）基因作为游离总 DNA 标志物在妊娠早期非侵入性检测胎儿三体 18 的准确性。
方法/主要发现：对 66 名孕妇的血浆进行了巢式病例对照研究，其中 11 名孕妇怀有三体 18 胎儿，55 名孕妇怀有正常胎儿。与对照组相比，患有三体 18 胎儿的孕妇的 U-maspin 浓度中位数显著升高（27.2 比 6.7 拷贝/ml；P<0.001）。患有三体 18 胎儿的孕妇的 M-maspin 浓度中位数也显著高于对照组（96.9 比 19.5 拷贝/ml，P<0.001）。U-maspin 和 M-maspin 浓度用于非侵入性胎儿三体 18 检测的特异性分别为 96.4%和 74.5%，敏感性为 90.9%。
我们的结果表明，U-maspin 和 M-maspin 浓度可能是妊娠早期非侵入性检测胎儿三体 18 的潜在生物标志物，与胎儿的性别和遗传变异无关。
