Lau Tai-Wah, Leung Tse N, Chan Lisa Y S, Lau Tze K, Chan K C Allen, Tam Wing H, Lo Y M Dennis
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR.
Clin Chem. 2002 Dec;48(12):2141-6.
Increased fetal DNA in maternal plasma/serum has been reported in pregnancies complicated by preeclampsia. We hypothesized that impaired clearance of fetal DNA might contribute, at least in part, to the above-mentioned phenomenon.
We studied 7 preeclamptic and 10 control pregnant women. All had male fetuses. Serial blood samples were obtained from before delivery to 6 h postpartum. Male fetal DNA in maternal plasma was measured by real-time quantitative PCR for the SRY gene on the Y chromosome.
The median fetal DNA concentrations before delivery were significantly higher in the preeclamptic women than in the controls (521 vs 227 genome-equivalents/mL for preeclamptic and control women, respectively; Mann-Whitney rank-sum test, P = 0.017). The median fetal DNA concentrations at 6 h after delivery were also significantly different between the two groups (208 vs 0 genome-equivalents/mL for preeclamptic and control women, respectively; Mann-Whitney rank-sum test, P = 0.002). A first-order clearance model was found to best describe the kinetics of maternal plasma fetal DNA clearance. Moreover, we observed a significant difference in the median apparent clearance half-lives of fetal DNA between the preeclamptic women (114 min) and controls (28 min; Mann-Whitney rank-sum test, P = 0.007).
This study represents the first documentation of impaired fetal DNA clearance from maternal plasma in preeclampsia. Such an abnormality in circulating DNA clearance may also be present in other medical conditions associated with quantitative aberrations in circulating DNA concentrations.
已有报道称,子痫前期孕妇血浆/血清中的胎儿DNA含量增加。我们推测,胎儿DNA清除受损可能至少部分导致了上述现象。
我们研究了7例子痫前期孕妇和10例对照孕妇。所有孕妇均怀有男性胎儿。从分娩前至产后6小时采集系列血样。采用实时定量PCR法检测母血血浆中Y染色体上SRY基因的男性胎儿DNA。
子痫前期孕妇分娩前胎儿DNA浓度中位数显著高于对照组(子痫前期孕妇和对照组分别为521和227基因组当量/mL;Mann-Whitney秩和检验,P = 0.017)。两组产后6小时的胎儿DNA浓度中位数也有显著差异(子痫前期孕妇和对照组分别为208和0基因组当量/mL;Mann-Whitney秩和检验,P = 0.002)。发现一级清除模型最能描述母血血浆中胎儿DNA清除的动力学。此外,我们观察到子痫前期孕妇与对照组胎儿DNA的中位表观清除半衰期存在显著差异(分别为114分钟和28分钟;Mann-Whitney秩和检验,P = 0.007)。
本研究首次证明子痫前期孕妇母血血浆中胎儿DNA清除受损。这种循环DNA清除异常也可能存在于其他与循环DNA浓度定量异常相关的疾病中。