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双胎妊娠中母体外周血信使 RNA:绒毛膜性及严重双胎输血综合征(TTTS)的影响。

Maternal cell-free messenger RNA in twin pregnancies: the effects of chorionicity and severe twin to twin transfusion syndrome (TTTS).

机构信息

Fetal Medicine Centre, Birmingham Women's Foundation Trust, Edgbaston, Birmingham, UK.

出版信息

Acta Obstet Gynecol Scand. 2012 Oct;91(10):1206-11. doi: 10.1111/j.1600-0412.2012.01507.x. Epub 2012 Aug 21.

DOI:10.1111/j.1600-0412.2012.01507.x
PMID:22862673
Abstract

OBJECTIVE

To investigate the effects of chorionicity and severe twin to twin transfusion (TTTS) on maternal circulating cell-free messenger RNA (cf-mRNA).

DESIGN

Prospective cohort study.

SETTING

A UK tertiary referral Fetal Medicine Center.

POPULATION

All monochorionic (MC) twins complicated by severe TTTS (n= 23) and a cohort of uncomplicated dichorionic (DC) (n= 10) and MC (n= 7) pregnancies, between October 2006 and December 2007.

METHODS

Maternal cf-mRNA encoding glyceraldehyde 3-phosphate dehydrogenase (GAPDH), vascular endothelial growth factor receptor 1(VEGFR-1(Flt-1)), vascular endothelial growth factor A (VEGF-A), Endoglin, placental growth factor (PlGF), tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (Tie-1), angiopoietin 1 (Ang-1) and angiopoietin 2 (Ang-2) were measured by a quantitative two-step real-time PCR assay after extraction from maternal plasma.

RESULTS

The amounts of cf-mRNA detectable are reported for uncomplicated DC, MC and TTTS pregnancies, respectively: GAPDH - 80, 100 and 96%; VEGFR-1 - 10, 0 and 26%; VEGF-A- 80, 71 and 96%; Endoglin-70, 71 and 91%; PlGF-70, 57, 26%; Tie-1 0, 43, 0%; Ang-1 71, 50 and 60% and Ang-2 83, 50 and 89%. There was a significant difference in VEGF-A (medians DC -337.3, MC - 390.8, TTTS - 618.6 copies/mL plasma p= 0.024), Endoglin (medians DC-14.49, MC-1171, TTTS - 2896 copies/mL plasma p= 0.027) and Ang-2 (medians DC-13.66, MC-8.49, TTTS 44.80 copies/mL plasma p= 0.007).

CONCLUSION

Maternal cf-mRNA could be reliably detected for GAPDH, PlGF, VEGF-A, Endoglin, Ang-1 and Ang-2 in twin pregnancies and a significant difference was demonstrated in VEGF-A, Endoglin and Ang-2 between uncomplicated twins and MC twin pregnancies complicated by TTTS. If such alterations in maternal cf-mRNA precede the onset of clinically apparent disease, this may be used as an adjuvant blood test to complement ultrasound screening.

摘要

目的

研究绒毛膜性和严重双胎输血综合征(TTTS)对母体循环游离信使 RNA(cf-mRNA)的影响。

设计

前瞻性队列研究。

地点

英国一家三级转诊胎儿医学中心。

人群

所有复杂性单绒毛膜(MC)双胎妊娠伴严重 TTTS(n=23)以及一组单纯性双绒毛膜(DC)(n=10)和 MC(n=7)妊娠,于 2006 年 10 月至 2007 年 12 月期间纳入研究。

方法

采用两步实时定量 PCR 法从母体血浆中提取甘油醛 3-磷酸脱氢酶(GAPDH)、血管内皮生长因子受体 1(VEGFR-1(Flt-1))、血管内皮生长因子 A(VEGF-A)、内皮糖蛋白(Endoglin)、胎盘生长因子(PlGF)、含免疫球蛋白样和表皮生长因子样结构域的酪氨酸激酶 1(Tie-1)、血管生成素 1(Ang-1)和血管生成素 2(Ang-2)的 cf-mRNA。

结果

未合并 DC、MC 和 TTTS 妊娠时,cf-mRNA 的检测量分别为:GAPDH-80、100 和 96%;VEGFR-1-10、0 和 26%;VEGF-A-80、71 和 96%;Endoglin-70、71 和 91%;PlGF-70、57 和 26%;Tie-1-0、43 和 0%;Ang-1-71、50 和 60%和 Ang-2-83、50 和 89%。VEGF-A(中位数 DC-337.3、MC-390.8、TTTS-618.6 拷贝/mL 血浆,p=0.024)、Endoglin(中位数 DC-14.49、MC-1171、TTTS-2896 拷贝/mL 血浆,p=0.027)和 Ang-2(中位数 DC-13.66、MC-8.49、TTTS-44.80 拷贝/mL 血浆,p=0.007)在 MC 双胎妊娠伴 TTTS 与未合并 TTTS 的 DC 和 MC 双胎妊娠之间存在显著差异。

结论

GAPDH、PlGF、VEGF-A、Endoglin、Ang-1 和 Ang-2 可在双胎妊娠中可靠地检测到母体 cf-mRNA,并且在未合并 TTTS 的 MC 双胎妊娠与 TTTS 合并的 MC 双胎妊娠之间,VEGF-A、Endoglin 和 Ang-2 存在显著差异。如果母体 cf-mRNA 的这种改变先于临床明显疾病的发生,那么它可能作为辅助血液检查,以补充超声筛查。

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