Single Nucleotide Polymorphisms Related to HPA Axis Reactivity

DeRijk, Roel H.

doi:10.1159/000216192

Cited by 130 publications

(102 citation statements)

References 178 publications

(114 reference statements)

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“…Genetics of stress responses Basal activity of the HPA axis and the response to stress are strongly influenced by genetic factors Redei, 2008;DeRijk, 2009). Pig populations show much functional variation (e.g.…”

Section: Genetics and The Hpa Axismentioning

confidence: 99%

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Breeding for robustness: the role of cortisol

Mormède

Foury

Terenina

et al. 2011

Animal

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Robustness in farm animals was defined by Knap as 'the ability to combine a high production potential with resilience to stressors, allowing for unproblematic expression of a high production potential in a wide variety of environmental conditions'. The importance of robustness-related traits in breeding objectives is progressively increasing towards the production of animals with a high production level in a wide range of climatic conditions and production systems, together with a high level of animal welfare. Current strategies to increase robustness include selection for 'functional traits', such as skeletal and cardiovascular integrity, disease resistance and mortality in various stages. It is also possible to use global evaluation of sensitivity to the environment (e.g. reaction norm analysis or canalization), but these techniques are difficult to implement in practice. The hypothalamic-pituitaryadrenocortical (HPA) axis is the most important stress-responsive neuroendocrine system. Cortisol (or corticosterone) released by the adrenal cortices exerts a large range of effects on metabolism, the immune system, inflammatory processes and brain function, for example. Large individual variations have been described in the HPA axis activity with important physiopathological consequences. In terms of animal production, higher cortisol levels have negative effects on growth rate and feed efficiency and increase the fat/lean ratio of carcasses. On the contrary, cortisol has positive effects on traits related to robustness and adaptation. For instance, newborn survival was shown to be directly related to plasma cortisol levels at birth, resistance to bacteria and parasites are increased in animals selected for a higher HPA axis response to stress, and tolerance to heat stress is better in those animals that are able to mount a strong stress response. Intense selection for lean tissue growth during the last decades has concomitantly reduced cortisol production, which may be responsible for the negative effects of selection on piglet survival. One strategy to improve robustness is to select animals with higher HPA axis activity. Several sources of genetic polymorphism have been described in the HPA axis. Hormone production by the adrenal cortices under stimulation by adrenocorticotropin hormone is a major source of individual differences. Several candidate genes have been identified by genomic studies and are currently under investigation. Bioavailability of hormones as well as receptor and post-receptor mechanisms are also subject to individual variation. Integration of these different sources of genetic variability will allow the development of a model for marker-assisted selection to improve animal robustness without negative side effects on production traits.

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Section: Genetics and The Hpa Axismentioning

confidence: 99%

“…Harizi et al, 2007, in mice). In humans and laboratory animals, numerous molecular variations have been described in the sequence of receptors, with functional consequences for health and disease (van Rossum and Lamberts, 2004;DeRijk, 2009), but very little information is available in farm animal species (Perreau et al, 1999).…”

Section: Genetics and The Hpa Axismentioning

confidence: 99%

Breeding for robustness: the role of cortisol

Mormède

Foury

Terenina

et al. 2011

Animal

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“…Similarly, both NR3C2 polymorphisms, rs5522 and rs2070951, are also located in the same LD block [19] and have weak but still significant LD to each other (D'=0.59, r 2 =0.52, P<0.01). Since the intermarker pair-wise LD is moderate, the haplotype analysis is unlikely to add much to the association results.…”

Section: Gr Glucocorticoid Receptor; Mr Mineralocorticoid Receptor;mentioning

confidence: 96%

“…The magnitude of the HPA response was shown to be deeply modulated by polymorphic variants of genes encoding the HPA axis components [19,20]. Indeed, we can hypothesize that HPA axis genetic polymorphisms may be also involved in controlling interpersonal variances in the coping capacity to prenatal stress.…”

Section: Introductionmentioning

confidence: 99%

“…Both receptors are located in the hippocampus, a region of the brain limbic system, in which cortisol could affect the production and release of various neurotransmitters and in turn influence human behavioral and personality traits [19]. Therefore, we can hypothesize that functionally relevant NR3C1 and NR3C2 polymorphisms, which alter the HPA axis activity and influence cortisol levels, can also be implicated in controlling capacity to cope with prenatal stress.…”

Section: Introductionmentioning

confidence: 99%

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Common variants of the mineralocorticoid and glucocorticoid receptor genes may contribute to pregnancy-related anxiety: a pilot study

2012

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AbstractThe hypothalamic-pituitary-adrenal (HPA) axis overactivity is thought to contribute to increased vulnerability to maternal stress. We hypothesize that functionally relevant polymorphic variants of the glucocorticoid (NR3C1) and mineralocorticoid (NR3C2) receptor genes mediating biological effects of cortisol, a major stress hormone, could also modulate the capacity to cope with pregnancy-related anxiety. Genomic DNA from the blood of 42 women with pregnancy-related anxiety and 42 age-matched women with normal pregnancy (5–6th months of gestation) were genotyped for markers rs6195 and rs10482605 of NR3C1 and two NR3C2 polymorphisms (rs5522 and rs2070951) using a Taqman allele discrimination assay. Serum total cortisol was measured using an ELISA technique. The allele Ser363 of rs6195 (the N363S polymorphism of NR3C1) was found to be associated with a higher risk of maternal stress (odds ratio (OR)=5.27; P=0.001). For NR3C2, the allele Val180 of rs5522 (I180V) also showed association with increased risk of neonatal stress (OR=1.97; P=0.038). Both predisposing gene variants were also associated with significantly elevated levels of cortisol in normally pregnant women and females with pregnancy-related anxiety. Our results suggest that pregnancy-related anxiety can be modulated by variants of NR3C1 and NR3C2 associated with increased basal cortisol levels. Thus, our findings provide evidence in support of the suggestion that elevated cortisol levels and HPA axis hyperactivity are implicated in pregnancy-related anxiety.

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Glucocorticoid receptor haplotype is associated with a decreased risk of delirium in the elderly

Manenschijn

Rossum

Jetten

et al. 2011

American J of Med Genetics Pt B

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Delirium is the most common mental disorder at older age in hospitals after acute admission. The pathogenesis of delirium is largely unknown. Hyperactivity of the hypothalamic-pituitary-adrenal axis, leading to increased cortisol levels, has been suggested to play a role in the development of delirium. The effects of cortisol, the most important glucocorticoid (GC) in humans, are mainly mediated by the GC receptor (GR). Several polymorphisms in the GR gene that alter the GC sensitivity are known. The aim of this study was to study the role of these GR polymorphisms in delirium in elderly patients. Patients aged 65 years and older admitted to the medical department or scheduled for hip surgery were included. Delirium was diagnosed using the Confusion Assessment Method. Five single nucleotide polymorphisms in the GC receptor gene were genotyped and haplotypes were constructed. Delirium was associated with impaired cognitive (P < 0.001) and functional function (P < 0.001), as well as with older age (P < 0.001). Homozygous carriers of haplotype 4, characterized by the presence of the BclI and TthIIII minor alleles, had a 92% decreased risk of developing delirium (P = 0.02), independent of age, cognitive, and functional state. Homozygous carriage of the BclI-TthIIII haplotype of the GR gene is related to a reduced risk of developing delirium. This suggests that altered GC signaling may be involved in the pathogenesis and development of delirium in the elderly.

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Single Nucleotide Polymorphisms Related to HPA Axis Reactivity

Cited by 130 publications

References 178 publications

Breeding for robustness: the role of cortisol

Breeding for robustness: the role of cortisol

Common variants of the mineralocorticoid and glucocorticoid receptor genes may contribute to pregnancy-related anxiety: a pilot study

Glucocorticoid receptor haplotype is associated with a decreased risk of delirium in the elderly

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