title: Microarray screening for novel preeclampsia biomarker candidates.
abstract: BACKGROUND
  Our aim was to identify novel biomarker candidates for the near-term prediction of preeclampsia in a homogenous collective. In this study, we screened at the genome-wide level for gene expression in placental villous tissue from patients with severe preeclampsia in comparison to normal healthy pregnancies.
  
  
  METHODS
  Total RNA was extracted from placental villous tissue from 9 preeclamptic patients and 7 normotensive controls after scheduled cesarean sections. After sample pooling, gene expression analysis was performed using six Affymetrix Human Gene 1.0 ST arrays, followed by quantitative RT-PCR and validation of selected markers in the serum of patients at the protein level.
  
  
  RESULTS
  In total, 896 significantly differentially expressed genes were identified (p ≤ 0.05). After restricting these to molecules present in the circulation, 9 upregulated and 5 downregulated genes were selected. Four of them (β-hCG, HTRA4, LHB1, all upregulated; and NOX4, downregulated) were validated by quantitative real-time RT-PCR. Finally, the maternal plasma protein levels of 2 of these genes (LHB and β-hCG) were confirmed to be significantly different between preeclampsia cases and controls.
  
  
  CONCLUSIONS
  We identified 14 potential new biomarker candidates for preeclampsia and validated 4 of them by quantitative RT-PCR and 2 of them with subsequent serum protein analyses. Further studies will assess the optimal marker combination for the imminent prediction of impending preeclampsia.
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Basel, Basel, Switzerland. olapaire@uhbs.ch
authors.forename: Olav
authors.initials: O
authors.lastname: Lapaire
authors.forename: Simon
authors.initials: S
authors.lastname: Grill
authors.forename: Sebastien
authors.initials: S
authors.lastname: Lalevee
authors.forename: Varaprasad
authors.initials: V
authors.lastname: Kolla
authors.forename: Irene
authors.initials: I
authors.lastname: Hösli
authors.forename: Sinuhe
authors.initials: S
authors.lastname: Hahn
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood / Q000235:genetics; D002824:Chorionic Villi / Q000737:chemistry; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D037101:Luteinizing Hormone, beta Subunit / Q000097:blood / Q000235:genetics; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011225:Pre-Eclampsia / Q000097:blood / Q000235:genetics*; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics; D013557:Switzerland; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D005819:Genetic Markers; D037101:Luteinizing Hormone, beta Subunit; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; D012697:Serine Endopeptidases