Seven placental transcripts characterize HELLP-syndrome.
The human placenta is prerequisite for the development of gestational hypertensive diseases like early-onset preeclampsia (PE) and Hemolysis, Elevated Liver enzymes and Low platelets (HELLP) syndrome. Both syndromes are associated with extensive maternal and perinatal mortality, and morbidity with life long consequences. We aimed to investigate differences in gene expression between placental tissue obtained from normotensive pregnant women and women with PE and HELLP syndrome. Firstly, comparison of Serial Analysis of Gene Expression profiles of 28 weeks' control placenta (available after idiopathic premature delivery) to a HELLP/PE placenta matched for gestational age identified 404 differentially expressed transcripts. Secondly, using sqPCR, the expression levels of 37 of these transcripts were analyzed in placentas of 36 pregnant women, 22 with preeclampsia and HELLP syndrome. Thirdly, nearest centroid classification determined the HELLP specific molecular signature consisting of the upregulated expression of genes encoding the vascular endothelial growth factor receptor (FLT1), leptin (LEP), pappalysin 2 (PAPPA2), and WW domain containing transcription regulator 1 (WWTR1) combined with down regulated expression of the genes encoding cadherin-associated protein (CTNNAL), glutathione S-transferase pi (GSTP1) and calgranulin A (S100A8). This set discriminates HELLP placenta from control and PE placenta with a 24% misclassification rate (95% CI 8.3-41.9%), independent from known risk factors like parity and ethnicity. The transcripts involved correspond to diverse molecular pathways, exemplifying the multigenic molecular basis of the disorder. This distinct placental molecular signature suggests that HELLP is not a PE variant but a separate disease entity. Our data may prove fundamental for the further molecular analysis of PE and HELLP syndrome.
Buimer
M
M
Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands.
Keijser
R
R
Jebbink
J M
JM
Wehkamp
D
D
van Kampen
A H C
AH
Boer
K
K
van der Post
J A M
JA
Ris-Stalpers
C
C
D000217:Acyltransferases; D000465:Algorithms; D040501:Calgranulin A / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D015723:Gene Library; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D017359:HELLP Syndrome / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism
C495274:CTNNAL1 protein, human; D040501:Calgranulin A; D020738:Leptin; D012333:RNA, Messenger; D014157:Transcription Factors; D051178:alpha Catenin; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; C430889:PAPPA2 protein, human; D011266:Pregnancy-Associated Plasma Protein-A