Tilbake til søkeresultatene

FRIMED-Klinisk medisin og folkehelse

Immune mechanisms and genetics associated with development of pre-eclampsia/eclampsia(PE/E)

Tildelt: kr 2,0 mill.

PE is regarded as a two-step disease, with poor placentation and placental hypoperfusion as the first step in pathogenesis. The recognition of fetal trophoblasts by maternal uterine (uNK) cells is fundamental in placental development. Observations suggest that the superficial trophoblast invasion in PE may be due to reduced/aberrant trophoblast expression of HLA-G and FasL (both inhibiting NK cell cytotoxicity). In contrast, other data suggest that PE is due to increased uNK cell cytotoxicity. In this pr oject, trophoblast, uNK cells and apoptosis in decidual tissues from pregnancies with poor placentation and controls will be studied (using immunohistochemical methods with mabs against relevant markers). In vitro NK cells cultures will be established fr om decidual tissues for functional analysis. Finally, expression of genes involved in interaction between trophoblasts/NK cells, HLA-G phenotypes and maternal susceptibility genes (PREG1, see below) will be assessed by microarray analysis. Placental hypo perfusion may evoke maternal responses including endothelial dysfunction and clinical PE manifestations occur (step 2). Genetic factors influence the character of maternal responses, and a region of maternal PE susceptibility on Chrom 2 (PREG1) has been i dentified. Association between genes located within PREG1 and disease will be studied in candidate gene study on cases with several PE pregnancies (n=266) and controls in the HUNT population. Further analysis of gene assossiations will be done in a family linkage study (n=150 PE families).

Budsjettformål:

FRIMED-Klinisk medisin og folkehelse

Temaer og emner

Ingen temaer knyttet til prosjektet