Mineralocorticoid receptor (MR) regulation in stress responsiveness and psychopathology: influence of single nucleotide polymorphisms (SNPs)

Liane Klok

The aim of my project is to investigate the role of MR expression in stress responsiveness and psychopathology. We want to know if SNPs in the MR promoter region have influence on MR expression and if they are related to stress-related phenotypes and disorders like depression. SNPs and haplotypes in the MR promoter region are tested for functionality -their effect on MR-gene promoter activity- in vitro with the help of reporter assays. In addition, these MR gene variants are tested for association with stress-related phenotypes among adults and elderly subjects. Furthermore, the expression of different MR splice variants is quantified and compared between different key regions of human post-mortem brain of depressed patients and non-depressed controls. Finally, we will verify whether the differences in MR expression that are found are due to variation in methylation of the DNA. We hypothesise that genetic variants in the MR promoter region influence its activity and therefore MR expression, and are related to differences in the vulnerability for psychopathology.