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The cardiovascular and hypothalamus-pituitary-adrenal axis response to stress is controlled by glucocorticoid receptor sequence variants and promoter methylation

Overview of attention for article published in Clinical Epigenetics, January 2016
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (83rd percentile)
  • Good Attention Score compared to outputs of the same age and source (77th percentile)

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Title
The cardiovascular and hypothalamus-pituitary-adrenal axis response to stress is controlled by glucocorticoid receptor sequence variants and promoter methylation
Published in
Clinical Epigenetics, January 2016
DOI 10.1186/s13148-016-0180-y
Pubmed ID
Authors

Ting Li-Tempel, Mauro F. Larra, Estelle Sandt, Sophie B. Mériaux, Andrea B. Schote, Hartmut Schächinger, Claude P. Muller, Jonathan D. Turner

Abstract

Gender, genetic makeup, and prior experience interact to determine physiological responses to an external perceived stressor. Here, we investigated the contribution of both genetic variants and promoter methylation of the NR3C1 (glucocorticoid receptor) gene to the cardiovascular and hypothalamus-pituitary-adrenal (HPA) axis response to the socially evaluated cold pressor test (seCPT). Two hundred thirty-two healthy participants were recruited and underwent the experiment. They were randomly assigned to either the seCPT group (cold water) or a control group (warm water). The seCPT group had a clear stress reaction; salivary cortisol levels and peak systolic and diastolic blood pressure all increased significantly compared to the control group. GR genotype (TthIIII, NR3C1-I, 1H, E22E, R23K, BclI and 9beta) and methylation data were obtained from 218 participants. Haplotypes were built from the GR genotypes, and haplotype 2 (minor allele of BclI) carriers had a higher cortisol response to the seCPT in comparison to non-carriers (20.77 ± 13.22; 14.99 ± 8.42; p = 0.034), as well as independently of the experimental manipulation, higher baseline heart rate (72.44 ± 10.99; 68.74 ± 9.79; p = 0.022) and blood pressure (115.81 ± 10.47; 111.61 ± 10.74; p = 0.048). Average methylation levels throughout promoter 1F and 1H were low (2.76 and 1.69 %, respectively), but there was a strong correlation between individual CpGs and the distance separating them (Pearson's correlation r = 0.725, p = 3.03 × 10(-26)). Higher promoter-wide methylation levels were associated with decreased baseline blood pressure, and when incorporated into a linear mixed effect model significantly predicted lower systolic and diastolic blood pressure evolution over time in response to the experimental manipulation. The underlying genotype significantly predicted methylation levels; particularly, the homozygous BclI minor allele was associated with higher methylation in promoter 1H (p = 0.042). This is one of the first studies linking epigenetic modifications of the GR promoter, receptor genotype and physiological measures of the stress response. At baseline, there were clear genetic and epigenetic effects on blood pressure. The seCPT induced a strong cardiovascular and HPA axis response, and both systems were affected by the functional genetic variants, although methylation also predicted blood pressure reactivity. The return to baseline was predominantly influenced by the genomic sequence. Overall, the physiological response to the seCPT is controlled by an exquisite mix of genetic and epigenetic factors.

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X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 120 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Chile 1 <1%
United States 1 <1%
Luxembourg 1 <1%
Unknown 117 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 22 18%
Student > Master 17 14%
Student > Bachelor 15 13%
Researcher 9 8%
Student > Doctoral Student 7 6%
Other 26 22%
Unknown 24 20%
Readers by discipline Count As %
Psychology 16 13%
Agricultural and Biological Sciences 14 12%
Biochemistry, Genetics and Molecular Biology 14 12%
Medicine and Dentistry 13 11%
Nursing and Health Professions 8 7%
Other 24 20%
Unknown 31 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 June 2016.
All research outputs
#4,207,698
of 25,374,917 outputs
Outputs from Clinical Epigenetics
#300
of 1,436 outputs
Outputs of similar age
#68,284
of 405,488 outputs
Outputs of similar age from Clinical Epigenetics
#8
of 36 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. Compared to these this one has done well and is in the 83rd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,436 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one has done well, scoring higher than 79% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 405,488 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 83% of its contemporaries.
We're also able to compare this research output to 36 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 77% of its contemporaries.