Polymorphisms of genes related to the hypothalamic-pituitary-adrenal axis influence the cortisol awakening response as well as self-perceived stress

•Genes regulating the HPA axis were investigated with regard to the cortisol awakening response (CAR) & self-perceived stress.•GR polymorphisms showed gender-dependent association with physiological (CAR) & psychological (perceived stress) indices.•CAR AUCi was affected by the polymorphisms of different genes whereas CAR AUCg did not show any association.•GR polymorphisms together with CAR & self reports on perceived stress might be useful indicators for basal HPA axis activity.

The hypothalamus-pituitary-adrenal (HPA) axis is a crucial endocrine system for coping with stress. A reliable and stable marker for the basal state of that system is the cortisol awakening response (CAR). We examined the influence of variants of four relevant candidate genes; the mineralocorticoid receptor gene (MR), the glucocorticoid receptor gene (GR), the serotonin transporter gene (5-HTT) and the gene encoding the brain-derived neurotrophic factor (BDNF) on CAR and self-perceived stress in 217 healthy subjects. We found that polymorphisms of GR influenced both, the basal state of the HPA axis as well as self-perceived stress. MR only associated with self-perceived stress and 5-HTT only with CAR. BDNF did not affected any of the investigated indices. In summary, we suggest that GR variants together with the CAR and supplemented with self reports on perceived stress might be useful indicators for the basal HPA axis activity.