Preeclampsia is a common, pregnancy-specific vascular disorder characterised by hypertension and proteinuria. A recent report suggested association of the STOX1 gene on chromosome 10q22.1 with preeclampsia in the Dutch population. Here, we present a comprehensive assessment of STOX1 as a candidate gene for preeclampsia in the Finnish population by re-examining our previous genetic linkage analysis results for both chromosome 10 and paralogous loci, by genotyping representative markers in a nationwide data set, and by studying STOX1 expression in placentas from preeclamptic and uncomplicated pregnancies. In conclusion, we are unable to validate STOX1 as a common preeclampsia susceptibility gene.

BackgroundDystocia, difficult labour, is a common but also complex problem during childbirth. It can be attributed to either weak contractions of the uterus, a large infant, reduced capacity of the pelvis or combinations of these. Previous studies have indicated that there is a genetic component in the susceptibility of experiencing dystocia. The purpose of this study was to identify susceptibility genes in dystocia.MethodsA total of 104 women in 47 families were included where at least two sisters had undergone caesarean section at a gestational length of 286 days or more at their first delivery. Study of medical records and a telephone interview was performed to identify subjects with dystocia. Whole-genome scanning using Affymetrix genotyping-arrays and non-parametric linkage (NPL) analysis was made in 39 women exhibiting the phenotype of dystocia from 19 families. In 68 women re-sequencing was performed of candidate genes showing suggestive linkage: oxytocin (OXT) on chromosome 20 and oxytocin-receptor (OXTR) on chromosome 3.ResultsWe found a trend towards linkage with suggestive NPL-score (3.15) on chromosome 12p12. Suggestive linkage peaks were observed on chromosomes 3, 4, 6, 10, 20. Re-sequencing of OXT and OXTR did not reveal any causal variants.ConclusionsDystocia is likely to have a genetic component with variations in multiple genes affecting the patient outcome. We found 6 loci that could be re-evaluated in larger patient cohorts.

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The rho-associated coiled-coil protein kinase 2 (ROCK2) gene has been suggested to associate with general hypertension and is therefore a plausible functional candidate gene for pre-eclampsia. ROCK2 maps to chromosome 2p25, which we have implicated previously in a linkage study of pre-eclampsia. We have re-sequenced exons and putative promoter region of ROCK2 in up to 30 pre-eclampsia patients and 22 controls and genotyped putative functional single-nucleotide polymorphisms (SNPs) as well as tagging SNPs from HapMap in a Finnish case-control data set-340 affected and 357 matched control individuals-for a genetic association study of ROCK2 in pre-eclampsia. Even though several new SNPs were discovered, we did not detect significant allelic or haplotypic association between ROCK2 and pre-eclampsia. We assessed ROCK2 expression in placentas by microarray analysis, but no significant expression differences were observed when comparing preeclamptic and normotensive pregnancies. We conclude that common genetic variation in ROCK2 is unlikely to make a major contribution to the risk of pre-eclampsia, but cannot exclude the possibility of having missed non-coding functional variants or rare coding variants.