Molecular analysis of the M2/ANXA5 haplotype as a new marker for infertility and thrombophilia predisposition

Basic data for this project

Description

Thrombophilia predispositions are a recognized factor for miscarriages and placental obstetric complications. Significant share of these conditions are hereditary. A recently found gene variant, M2/ANXA5, has been confirmed to associate with recurrent pregnancy loss (RPL), thrombophilia related obstetric complications, venous and supposedly arterial thromboses as well. Working hypothesis of this project is that proposed reduced expression of ANXA5 through carriage of the M2 haplotype can be a risk factor for the relevant clinical phenotypes. The goal is to confirm factors that modulate the expression of annexin A5, placental anticoagulant protein, in the relevant tissue and identify synthetic analogs. Following strategies will be pursued: a) ANXA5 expression studies on mRNA and protein level in chorionic villi of aborted material in an extended patient cohort; b) genotyping of maternal and fetal material for ANXA5 promoter alleles and correlation with expression levels, pregnancy stage and thrombophilia related phenotypes; c) analysis of steroid dependence of ANXA5 expression in a cell culture model; d) screening of factors that can modulate ANXA5 expression using chemical libraries of bioactive compounds; e) treatment of a murine heterozygous lack of function (ANXA5 K/O) model with compounds that activate ANXA5 expression.