Pregnancy associated plasma protein-A2: A novel biomarker for down syndrome

S. Munnangi, S. J. Gross, R. Madankumar, G. Salcedo, S. E. Reznik

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Introduction: In an effort to improve prenatal screening for Trisomy 21, we evaluated pregnancy associated plasma protein-A2 (PAPP-A2) as a potential novel second trimester biomarker for Trisomy 21.

Methods: Trisomy 21 and normal control mid-trimester placental samples were subjected to quantitative rt PCR analysis of seven genes we had previously found to be differentially expressed in Trisomy 21 placentae. The localization and differential expression of PAPP-A2 in second trimester placentae from normal and Trisomy 21 pregnancies was determined by immunohistochemistry. PAPP-A2 maternal serum protein levels in ten Trisomy 21 and ten diploid pregnancies were compared by Western blotting. Maternal serum PAPP-A2 levels were measured in 30 Down syndrome cases and 142 normal controls, using ELISA. Regression analysis was used to determine the correlation of PAPP-A2 with other existing markers of Trisomy 21.

Results: PAPP-A2 (aka PLAC 3) mRNA and protein expression were both increased in Down syndrome placentae as compared to diploid placentae. PAPP-A2 was also increased in maternal serum from Down syndrome pregnancies as compared to diploid pregnancies. PAPP-A2 expression correlated weakly with established markers. Discussion: This work takes advantage of our previously performed systematic approach to the discovery of novel maternal serum biomarkers for Trisomy 21, using cDNA microarray analysis. Beginning with the validation of the microarray results, we have tracked PAPP-A2 overexpression in Down syndrome from placental mRNA to maternal serum protein.

Conclusion: PAPP-A2 could serve as an additional maternal serum marker in prenatal screening for Trisomy 21.

Original languageEnglish (US)
Pages (from-to)900-906
Number of pages7
JournalPlacenta
Volume35
Issue number11
DOIs
StatePublished - Nov 1 2014

Keywords

  • Pregnancy associated plasma protein-A2 Biomarker Down syndrome Placenta Maternal serum Second trimester

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Developmental Biology

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