Vascular associated gene variants in patients with preeclampsia: results from the Danish National Birth Cohort

Abstract

Objective: Preeclampsia has been linked to subsequent vascular disease with many shared predisposing factors. We investigated the association between severe preeclampsia, and its subtypes, and specific vascular-related polymorphisms.

Design: The study was a retrospective nested case-cohort design.

Setting: Pregnant Danish women participating in the Danish National Birth Cohort. Population. 263 cases of severe preeclampsia and 1851 random controls were selected from the Danish National Birth Cohort.

Methods: We validated all cases of severe preeclampsia and genotyped for 108 single nucleotide polymorphisms (SNPs) that were selected based on previous publications on the association with vascular disease. Logistic models were used for statistical analyses.

Main outcome measures: Maternal polymorphisms in genomic models.

Results: We found 17 of 108 SNPs associated with severe preeclampsia (p < 0.05). Women homozygous for the rs1799983 in NOS3 were 1.6-fold [95% confidence interval (CI) 1.0-2.4] more likely to develop severe preeclampsia. Women homozygous for the rs1010 SNP in VAMP8 were twofold (95%CI 1.1-3.5) more likely to deliver preterm when preeclampsia was present. Women homozygous for the rs10811661 SNP were 2.1-fold (95%CI 1.1-3.9) more likely to develop severe preeclampsia and 3.7-fold (95%CI 1.1-12.4) more likely to deliver a small-for-gestational age child when preeclampsia was present. All associations are available as Supporting Information.

Conclusion: We found several vascular-associated SNPs linked to severe preeclampsia; however, most of these associations are probably by pure chance, which warrants replication and further translational research. To date, no specific SNP has yet proven valuable in a clinical setting in predicting preeclampsia.