278-POS

Abstract

Objectives Preeclampsia (PE) is a gestational disease classified by reproducible hypertension (HT) with proteinuria occurring in 2–8% of pregnancies. The heterogenous disease includes severe outcomes for mother and fetus. After PE both women and children demonstrate doubled risk of atherothrombotic cardiovascular disease (aCVD). The etiology of PE and pathophysiological links with aCVD are incomplete, but shared inflammatory processes are indicated. Our aim was to identify shared genetic risk factors for PE and aCVD development in a family-based PE cohort by determining presence of genetic changes associated with blood pressure (BP) regulation, inflammation and/or angiogenesis. Methods We selected 484 participants from the Norwegian PE Family Biobank which contain 138 families with increased occurrence of PE (including 338 parous women, 256 with PE). Individuals were phenotyped and phenotypic heritabilities were estimated for PE with subsets such as “born in PE pregnancy” (H2r = 0.25, p = 0.01), and related traits like aCVD (H2r = 0.31, p = 4.6 × 10 −3 ) and inflammatory conditions. Using two databases of genome-wide association studies we selected 115 SNPs associated either with BP regulation, inflammation and/or angiogenesis. A candidate SNP array was performed on Sequenom MassArray and genetic analyses were conducted using variance components and measured genotype procedures in SOLAR. Results The main finding was that individuals born in preeclamptic pregnancies demonstrated association with an intergenic SNP near BP regulator gene JAG1 ( p = 4.7 × 10 −4 ). This SNP is also associated with chronic HT ( p = 3.39 × 10 −3 ) in the families. Conclusions JAG1 has previously been associated with BP regulation in individuals with aCVD and was in our cohort found associated both with being born in a PE pregnancy and with chronic HT. Our finding demonstrates a novel genetic connection between PE and chronic HT. This is further supported by significant phenotypic heritability of these traits in the Norwegian families. Functional studies will be performed to elucidate the role of JAG1 in PE and aCVD. Disclosures L.V. Thomsen: None. N. McCarthy: None. P.E. Melton: None. K. Tollaksen: None. I. Lyslo: None. P. Solberg: None. L.T. Roten: None. O.K. Nygard: None. G. Cadby: None. R. Austgulen: None. E.K. Moses: None. A. Iversen: None. L. Bjorge: None.