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Hypothalamic-pituitary-adrenal (HPA) axis-related genetic variants influence the stress response

  • The physiological stress system includes the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary system (SAM). Parameters representing these systems such as cortisol, blood pressure or heart rate define the physiological reaction in response to a stressor. The main objective of the studies described in this thesis was to understand the role of the HPA-related genetic factors in these two systems. Genetic factors represent one of the components causing individual variations in physiological stress parameters. Five genes involved in the functioning of the HPA axis regarding stress responses are examined in this thesis. They are: corticotropin-releasing hormone (CRH), the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR), the 5-hydroxytryptamine-transporter-linked polymorphic region (5-HTTLPR) in the serotonin transporter (5-HTT) and the brain-derived neurotrophic factor (BDNF) gene. Two hundred thirty-two healthy participants were genotyped. The influence of genetic factors on physiological parameters, such as post-awakening cortisol and blood pressure was assessed, as well as the influence of genetic factors on stress reactivity in response to a socially evaluated cold pressor test (SeCPT). Three studies tested the HPA-related genes each on three different levels. The first study examined the influences of genotypes and haplotypes of these five genes on physiological as well as psychological stress indicators (Chapter 2). The second study examined the effects of GR variants (genotypes and haplotypes) and promoter methylation level on both the SAM system and the HPA axis stress reactivity (Chapter 3). The third study comprised the characterization of CRH promoter haplotypes in an in-vitro study and the association of the CRH promoter with stress indicators in vivo (Chapter 4).

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Author:Ting Li-Tempel
Referee:Jobst Dr. Meyer, Andrea Dr. Schote-Frese
Advisor:Jobst Dr. Meyer, Andrea Dr. Schote-Frese
Document Type:Doctoral Thesis
Language:English
Date of completion:2020/02/03
Publishing institution:Universit├Ąt Trier
Granting institution:Universit├Ąt Trier, Fachbereich 1
Date of final exam:2019/12/12
Release Date:2020/03/13
Tag:HPA; behavioral genetics; stress
Number of pages:166
Institutes:Fachbereich 1
Licence (German):License LogoCC BY-NC-ND: Creative-Commons-Lizenz 4.0 International

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