title: HLA gene expression is altered in whole blood and placenta from women who later developed preeclampsia.
abstract: Preeclampsia is a multisystem disease that significantly contributes to maternal and fetal morbidity and mortality. In this study, we used a non-biased microarray approach to identify dysregulated genes in maternal whole blood samples which may be associated with the development of preeclampsia. Whole blood samples were obtained at 28 wk of gestation from 5 women who later developed preeclampsia (cases) and 10 matched women with normotensive pregnancies (controls). Placenta samples were obtained from an independent cohort of 19 women with preeclampsia matched with 19 women with normotensive pregnancies. We studied gene expression profiles using Illumina microarray in blood and validated changes in gene expression in whole blood and placenta tissue by qPCR. We found a transcriptional profile differentiating cases from controls; 336 genes were significantly dysregulated in blood from women who developed preeclampsia. Functional annotation of microarray results indicated that most of the genes found to be dysregulated were involved in inflammatory pathways. While general trends were preserved, onlyHLA-Awas validated in whole blood samples from cases using qPCR (2.30- ± 0.9-fold change) whereas in placental tissueHLA-DRB1expression was found to be significantly increased in samples from women with preeclampsia (5.88- ± 2.24-fold change). We have identified thatHLA-Ais upregulated in the circulation of women who went on to develop preeclampsia. In placenta of women with preeclampsia we identified thatHLA-DRB1 isupregulated. Our data provide further evidence for involvement of theHLAgene family in the pathogenesis of preeclampsia.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom; and h.small.1@research.gla.ac.uk.
authors.forename: Heather Y
authors.initials: HY
authors.lastname: Small
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom; and.
authors.forename: Christine
authors.initials: C
authors.lastname: Akehurst
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom; and.|Kazan Federal University, Kazan, Russian Federation.
authors.forename: Liliya
authors.initials: L
authors.lastname: Sharafetdinova
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom; and.
authors.forename: Martin W
authors.initials: MW
authors.lastname: McBride
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom; and.
authors.forename: John D
authors.initials: JD
authors.lastname: McClure
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom; and.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Robinson
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom; and.
authors.forename: David M
authors.initials: DM
authors.lastname: Carty
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom; and.
authors.forename: Dilys J
authors.initials: DJ
authors.lastname: Freeman
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom; and.
authors.forename: Christian
authors.initials: C
authors.lastname: Delles
mesh_terms: D000328:Adult; D005260:Female; D005786:Gene Expression Regulation; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000097:blood* / Q000235:genetics*; D011247:Pregnancy; D059467:Transcriptome; D015854:Up-Regulation / Q000235:genetics
chemical_list: D006680:HLA Antigens
keywords: gene expression; microarray; placenta; preeclampsia