title: Differences and similarities in the transcriptional profile of peripheral whole blood in early and late-onset preeclampsia: insights into the molecular basis of the phenotype of preeclampsiaa.
abstract: OBJECTIVE
  Preeclampsia (PE) can be sub-divided into early- and late-onset phenotypes. The pathogenesis of these two phenotypes has not been elucidated. To gain insight into the mechanisms of disease, the transcriptional profiles of whole blood from women with early- and late-onset PE were examined.
  
  
  METHODS
  A cross-sectional study was conducted to include women with: i) early-onset PE (diagnosed prior to 34 weeks, n=25); ii) late-onset PE (after 34 weeks, n=47); and iii) uncomplicated pregnancy (n=61). Microarray analysis of mRNA expression in peripheral whole blood was undertaken using Affymetrix microarrays. Differential gene expression was evaluated using a moderated t-test (false discovery rate <0.1 and fold change >1.5), adjusting for maternal white blood cell count and gestational age. Validation by real-time qRT-PCR was performed in a larger sample size [early PE (n=31), late PE (n=72) and controls (n=99)] in all differentially expressed genes. Gene ontology analysis and pathway analysis were performed.
  
  
  RESULTS
  i) 43 and 28 genes were differentially expressed in early- and late-onset PE compared to the control group, respectively; ii) qRT-PCR confirmed the microarray results for early and late-onset PE in 77% (33/43) and 71% (20/28) of genes, respectively; iii) 20 genes that are involved in coagulation (SERPINI2), immune regulation (VSIG4, CD24), developmental process (H19) and inflammation (S100A10) were differentially expressed in early-onset PE alone. In contrast, only seven genes that encoded proteins involved in innate immunity (LTF, ELANE) and cell-to-cell recognition in the nervous system (CNTNAP3) were differentially expressed in late-onset PE alone. Thirteen genes that encode proteins involved in host defense (DEFA4, BPI, CTSG, LCN2), tight junctions in blood-brain barrier (EMP1) and liver regeneration (ECT2) were differentially expressed in both early- and late-onset PE.
  
  
  CONCLUSIONS
  Early- and late-onset PE are characterized by a common signature in the transcriptional profile of whole blood. A small set of genes were differentially regulated in early- and late-onset PE. Future studies of the biological function, expression timetable and protein expression of these genes may provide insight into the pathophysiology of PE.
authors.affiliation: Wayne State University/Hutzel Women’s Hospital, MI 48201, USA. tchaiwor@med.wayne.edu
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Amy
authors.initials: A
authors.lastname: Whitten
authors.forename: Adi L
authors.initials: AL
authors.lastname: Tarca
authors.forename: Gaurav
authors.initials: G
authors.lastname: Bhatti
authors.forename: Sorin
authors.initials: S
authors.lastname: Draghici
authors.forename: Piya
authors.initials: P
authors.lastname: Chaemsaithong
authors.forename: Jezid
authors.initials: J
authors.lastname: Miranda
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000328:Adult; D051927:CD24 Antigen / Q000235:genetics; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D020869:Gene Expression Profiling; D018392:Genomic Imprinting; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011225:Pre-Eclampsia / Q000097:blood* / Q000235:genetics*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D012313:RNA / Q000097:blood / Q000235:genetics; D062085:RNA, Long Noncoding / Q000097:blood / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics; D011951:Receptors, Complement / Q000235:genetics; D055815:Young Adult
chemical_list: C473800:ABCA13 protein, human; D018528:ATP-Binding Cassette Transporters; D051927:CD24 Antigen; C497889:CD24 protein, human; C464567:CNTNAP3 protein, human; C094335:H19 long non-coding RNA; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D062085:RNA, Long Noncoding; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; C414427:VSIG4 protein, human; C097051:epithelial membrane protein-1; D012313:RNA