Pregnancy associated plasma protein-A2: A novel biomarker for down syndrome |
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| Institution: | 1. Department of Pharmaceutical Sciences, St. John''s University, Queens, NY, USA;2. Natera, San Carlos, CA, USA;3. Department of Obstetrics and Gynecology, North Shore-LIJ Health System, Glen Cove, NY, USA;4. Endoclab, Porto, Portugal;5. Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA;6. Department of Obstetrics and Gynecology and Women''s Health, Albert Einstein College of Medicine, Bronx, NY, USA;1. Department of Obstetrics and Gynaecology, IRCCS San Raffaele Hospital, Vita-Salute University, 20132 Milan, Italy;2. Department of Obstetrics and Gynaecology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy;1. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Texas Health Science Center at Houston, USA;2. The Texas Fetal Center, 6410 Fannin, Suite 700, Houston Texas 77030, USA;1. Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;2. Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;3. Department of Biophysics, Pankab University, Chandigarh, India;1. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Mass;2. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Mass;3. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Mass;4. Broad Institute of MIT and Harvard, Cambridge, Mass;5. Department of Thoracic and Cardiovascular Surgery, Lahey Hospital and Medical Center, Burlington, Mass;1. Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung County, Taiwan;2. Department of Emergency Medicine, Chang Gung Memorial Hospital, No.6, W. Sec., Jiapu Rd., Puzih City, Chiayi County 613, Taiwan;3. Chang Gung University College of Medicine, No.5, Fusing St., Gueishan Township, Taoyuan County 333, Taiwan;4. Department of Emergency Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, No.123, Dapi Rd., Niaosong Dist., Kaohsiung City 833, Taiwan;5. Department of Occupation Medicine, Chang-Gung Memorial Hospital, Keelung Branch, Keelung 204, Taiwan |
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| Abstract: | IntroductionIn 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.MethodsTrisomy 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.ResultsPAPP-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.DiscussionThis 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.ConclusionPAPP-A2 could serve as an additional maternal serum marker in prenatal screening for Trisomy 21. |
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| Keywords: | Pregnancy associated plasma protein-A2 Biomarker Down syndrome Placenta Maternal serum Second trimester |
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