HLA gene expression is altered in whole blood and placenta from women who later developed preeclampsia

Small, H. Y., Akehurst, C., Sharafetdinova, L., McBride, M. W. , McClure, J. D. , Robinson, S. W., Carty, D. M., Freeman, D. J. and Delles, C. (2017) HLA gene expression is altered in whole blood and placenta from women who later developed preeclampsia. Physiological Genomics, 49(3), pp. 193-200. (doi:10.1152/physiolgenomics.00106.2016) (PMID:28130428) (PMCID:PMC5374453)

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Abstract

Preeclampsia is a multi-system 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 weeks 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; 236 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. Whilst general trends were preserved, only HLA-A was validated in whole blood samples from cases using qPCR (2.30 ± 0.9 fold change) whereas in placental tissue HLA-DRB1 expression was found to be significantly increased in samples from women with preeclampsia (5.88 ± 2.24 fold change). We have identified that HLA-A is up-regulated in the circulation of women who went on to develop preeclampsia. In placenta of women with preeclampsia we identified that HLA-DRB1 is up-regulated. Our data provide further evidence for involvement of the HLA gene family in the pathogenesis of preeclampsia.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Freeman, Dr Dilys and McBride, Dr Martin and Delles, Professor Christian and Sharafetdinova, Miss Liliia and Robinson, Mr Scott and Carty, Dr David and McClure, Dr John and Akehurst, Dr Christine
Authors: Small, H. Y., Akehurst, C., Sharafetdinova, L., McBride, M. W., McClure, J. D., Robinson, S. W., Carty, D. M., Freeman, D. J., and Delles, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Physiological Genomics
Publisher:American Physiological Society
ISSN:1094-8341
ISSN (Online):1531-2267
Published Online:27 January 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Physiological Genomics 49(3):193-200
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
557491EU-MASCARA - Biomarkers for Cardiovascular DiseaseChristian DellesEuropean Commission (EC)UNSPECIFIEDRI CARDIOVASCULAR & MEDICAL SCIENCES
595241Cardiovascular consequences of preeclampsia in women from the Generation Scotland: Scottish Family Health Study.Christian DellesScottish Executive Health Department (SEHHD-CSO)ETM/196RI CARDIOVASCULAR & MEDICAL SCIENCES
492454BHF 4 Year PhD ProgrammeAnna DominiczakBritish Heart Foundation (BHF)FS/12/66/30003RI CARDIOVASCULAR & MEDICAL SCIENCES