A genome-wide scan for preeclampsia in the Netherlands

Preeclampsia, hallmarked by de novo hypertension and proteinuria in pregnan cy, has a familial tendency. Recently, a large Icelandic genome-wide scan p rovided evidence for a maternal susceptibility locus for preeclampsia on ch romosome 2p13 which was confirmed by a genome scan from Australia and New Z ealand (NZ). The current study reports on a genome-wide scan of Dutch affec ted sib-pair families. In total 67 Dutch affected sib-pair families, compri sing at least two siblings with proteinuric preeclampsia, eclampsia or HELL P-syndrome, were typed for 293 polymorphic markers throughout the genome an d 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 sam e 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 leas t one sibling with HELLP syndrome (HELLP families), revealed two peaks with suggestive evidence for linkage in the non-HELLP families on chromosome 10 q (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 in creased 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 preecl ampsia families showed overlap with the second highest peak in the Australi an/NZ study. Results from our Dutch genome-wide scan indicate that HELLP sy ndrome might have a different genetic background than preeclampsia.