University of Oulu

Kaartokallio, T., Utge, S., Klemetti, M. M., Paananen, J., Pulkki, K., Romppanen, J., … Laivuori, H. (2018). Fetal Microsatellite in the Heme Oxygenase 1 Promoter Is Associated With Severe and Early-Onset Preeclampsia. Hypertension, 71(1), 95–102.

Fetal microsatellite in the heme oxygenase 1 promoter is associated with severe and early-onset preeclampsia

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Author: Kaartokallio, Tea1; Utge, Siddheshwar1; Klemetti, Miira M.1,2,3;
Organizations: 1Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
2Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
3Department of Obstetrics and Gynecology, South-Karelia Central Hospital, Lappeenranta, Finland
4Bioinformatics Center, University of Eastern Finland, Kuopio, Finland
5Department of Clinical Chemistry, University of Turku and, Saske Screening Center, Turku University Central Hospital, Turku, Finland
6Eastern Finland Laboratory Centre, Kuopio, Finland
7Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
8Minerva Foundation Institute for Medical Research, Helsinki, Finland
9Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland
10Children’s Hospital, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland
11PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
12Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
13Folkhälsan Institute of Genetics, Helsinki, and Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland
14Department of Medical & Molecular Genetics, King’s College London, London, UK
15Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK
16Department of Government services, National Institute for Health and Welfare, Helsinki, Finland
17Clinical Chemistry and Hematology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
18Institute for Molecular Medicine Finland, HiLIFE Unit, University of Helsinki, Helsinki, Finland
19Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
20Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 2 MB)
Persistent link:
Language: English
Published: Wolters Kluwer, 2018
Publish Date: 2019-11-19


Preeclampsia is a vascular pregnancy disorder that often involves impaired placental development. HO-1 (heme oxygenase 1, encoded by HMOX1) is a stress response enzyme crucial for endothelial and placental function. Long version of the guanine–thymine (GTn) microsatellite in the HMOX1 promoter decreases HO-1 expression, and the long maternal repeat is associated with late-onset preeclampsia. Our aim was to study whether the length of fetal repeat is associated with mother’s preeclampsia, whether the length of fetal and maternal repeats affect HO-1 levels in placenta and maternal serum, and whether HO-1 levels are altered in preeclampsia. We genotyped the repeat in the cord blood of 609 preeclamptic and 745 nonpreeclamptic neonates. HO-1 levels were measured in 36 placental samples, and in the first (222 cases/243 controls) and third (176 cases/53 controls) pregnancy trimester serum samples using enzyme-linked immunosorbent assay. The long fetal GTn repeat was associated with preeclampsia and its severe and early-onset subtypes. Interaction analysis suggested the maternal and fetal effects to be independent. Placental or serum HO-1 levels were not altered in preeclamptics, possibly reflecting heterogeneity of preeclampsia. Carriers of the long fetal and maternal repeats had lower placental and serum HO-1 levels, respectively, providing functional evidence for the association. We conclude that the long fetal GTn repeat may increase mother’s risk for especially severe and early-onset preeclampsia. The fetal and maternal risk alleles likely predispose to different disease subtypes.

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Series: Hypertension
ISSN: 0194-911X
ISSN-E: 1524-4563
ISSN-L: 0194-911X
Volume: 71
Issue: 1
Pages: 95 - 102
DOI: 10.1161/HYPERTENSIONAHA.117.10425
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Funding: The FINNPEC study was supported by Jane and Aatos Erkko Foundation, Päivikki and Sakari Sohlberg Foundation, Academy of Finland, Research Funds of the University of Helsinki, Government special state subsidy for health sciences at the Hospital District of Helsinki and Uusimaa, Finska Läkaresällskapet, Liv och Hälsa Foundation, Novo Nordisk Foundation, Finnish Foundation for Pediatric Research, Emil Aaltonen Foundation, Sigrid Jusélius Foundation, and Finnish Foundation for Laboratory Medicine. T. Kaartokallio was supported by Doctoral Programme in Biomedicine, Clinical Graduate Program, Research Foundation of the University of Helsinki and Biomedicum Helsinki Foundation. M.M. Klemetti was supported by the Research Foundation of the University of Helsinki, Paulo Foundation, Viipuri Tuberculosis Foundation, and the National Graduate School of Clinical Investigation. J. Kere is a recipient of The Royal Society Wolfson Research Excellence Award.
Copyright information: © 2017 American Heart Association, Inc. This is an Accepted Manuscript version of an article published in Hypertension Vol. 71:1. The Definitive Version of Record can be found online at: