Mineralocorticoid receptor gene variants : implications for stress, blood pressure and personality

Leeuwen, N. van

The project described in this thesis was designed to test if genetic variation in the mineralocorticoid receptor (MR) gene is a risk factor for developing major depression. First the MR-gene was screened for genetic variation. Two selected single nucleotide polymorphisms (SNPs) were tested for in vitro functionality at different levels including: protein and mRNA expression, transactivational capacity and ligand binding. Functionality in vitro was confirmed leading us to test their influence on electrolyte regulation, stress responsiveness and personality. First, in three different cohorts one SNP influenced blood pressure and salt regulation, as could be expected for the MR. Second, the SNPs were associated with the cortisol awaking response (CAR) after dexamethasone administration and with the cortisol and autonomic response following psychosocial stress. This indicates an important role for the MR in the regulation of the stress-response. Third in a relatively small cohort (n=150...Show moreThe project described in this thesis was designed to test if genetic variation in the mineralocorticoid receptor (MR) gene is a risk factor for developing major depression. First the MR-gene was screened for genetic variation. Two selected single nucleotide polymorphisms (SNPs) were tested for in vitro functionality at different levels including: protein and mRNA expression, transactivational capacity and ligand binding. Functionality in vitro was confirmed leading us to test their influence on electrolyte regulation, stress responsiveness and personality. First, in three different cohorts one SNP influenced blood pressure and salt regulation, as could be expected for the MR. Second, the SNPs were associated with the cortisol awaking response (CAR) after dexamethasone administration and with the cortisol and autonomic response following psychosocial stress. This indicates an important role for the MR in the regulation of the stress-response. Third in a relatively small cohort (n=150) the SNPs were not associated with mood and/or anxiety disorders but in the patient group there was an association with the personality trait neuroticism. We hypothesize that genetic variants in the MR-gene are determinants of vulnerability for psychiatric disorders.Show less

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Mineralocorticoid receptor gene variants : implications for stress, blood pressure and personality

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