A genome-wide scan for preeclampsia in the Netherlands

AMA Lachmeijer*, R Arngrimsson, EJ Bastiaans, ML Frigge, G Pals, S Sigurdardottir, H Stefansson, B Palsson, D Nicolae, A Kong, JG Aarnoudse, [No Value] Gulcher, GA Dekker, LP ten Kate, K Stefansson

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

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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.

    Original languageEnglish
    Pages (from-to)758-764
    Number of pages7
    JournalEuropean Journal of Human Genetics
    Volume9
    Issue number10
    Publication statusPublished - Oct-2001

    Keywords

    • preeclampsia
    • genetics
    • linkage
    • genome-wide scan
    • polymorphic markers
    • sib-pair
    • MATERNAL SUSCEPTIBILITY LOCUS
    • PRE-ECLAMPSIA
    • GENETIC SUSCEPTIBILITY
    • LINKAGE ANALYSIS
    • ALPHA GENE
    • PREGNANCY
    • HYPERTENSION
    • POLYMORPHISM
    • POPULATION
    • REGION

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