A genome-wide scan for preeclampsia in the Netherlands

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Abstract

Preeclampsia, hallmarked by de novo hypertension and proteinuria in pregnancy, has a familial tendency. Recently, a large Icelandic genome-wide scan provided evidence for a maternal susceptibility locus for preeclampsia on chromosome 2p13 which was confirmed by a genome scan from Australia and New Zealand (NZ). The current study reports on a genome-wide scan of Dutch affected sib-pair families. In total 67 Dutch affected sib-pair families, comprising at least two siblings with proteinuric preeclampsia, eclampsia or HELLP-syndrome, were typed for 293 polymorphic markers throughout the genome and linkage analysis was performed. The highest allele sharing lod score of 1.99 was seen on chromosome 12q at 109.5 cM. Two peaks overlapped in the same regions between the Dutch and Icelandic genome-wide scan at chromosome 3p and chromosome 15q. No overlap was seen on 2p. Re-analysis in 38 families without HELLP-syndrome (preeclampsia families) and 34 families with at least one sibling with HELLP syndrome (HELLP families), revealed two peaks with suggestive evidence for linkage in the non-HELLP families on chromosome 10q (lod score 2.38, D10S1432, 93.9 cM) and 22q (lod score 2.41, D22S685, 32.4 cM). The peak on 12q appeared to be associated with HELLP syndrome; it increased to a lod score of 2.1 in the HELLP families and almost disappeared in the preeclampsia families. A nominal peak on chromosome 11 in the preeclampsia families showed overlap with the second highest peak in the Australian/NZ study. Results from our Dutch genome-wide scan indicate that HELLP syndrome might have a different genetic background than preeclampsia.

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Acknowledgements

This study was financially supported by The Netherlands Organisation for Scientific Research (NWO; Grant no. 950-10-612), Health Research and Development Council (Grant no. 28-2593), Wellcome Trust, UK, Icelandic Research Council, University of Iceland Research Fund, and deCODE Genetics Inc. We wish to thank professor R.T. Geirsson MD PhD, Department of Obstetrics and Gynaecology of the University Hospital in Reykjavik, Iceland for his kind support and advice throughout the study and preparation of the manuscript. We also wish to thank Barry Pieters, Guido van de Berk, Soe Janssens and Bibi de Leeuw for their enthusiastic help in collecting family data and drawing blood from participants, and all gynaecologists of the 21 Dutch Hospitals that were willing to facilitate our recruitment of families. Finally, we gratefully acknowledge all families for their participation in this study.

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Correspondence to Augusta MA Lachmeijer or Kári Stéfansson.

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Lachmeijer, A., Arngrímsson, R., Bastiaans, E. et al. A genome-wide scan for preeclampsia in the Netherlands. Eur J Hum Genet 9, 758–764 (2001) doi:10.1038/sj.ejhg.5200706

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Keywords

  • preeclampsia
  • genetics
  • linkage
  • genome-wide scan
  • polymorphic markers
  • sib-pair

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