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Regulatory Polymorphisms in Human DBH Affect Peripheral Gene Expression and Sympathetic Activity

Overview of attention for article published in Circulation Research, December 2014
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (93rd percentile)
  • High Attention Score compared to outputs of the same age and source (93rd percentile)

Mentioned by

news
1 news outlet
blogs
2 blogs
twitter
1 tweeter

Citations

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15 Dimensions

Readers on

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23 Mendeley
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Title
Regulatory Polymorphisms in Human DBH Affect Peripheral Gene Expression and Sympathetic Activity
Published in
Circulation Research, December 2014
DOI 10.1161/circresaha.116.304398
Pubmed ID
Authors

Elizabeth S. Barrie, David Weinshenker, Anurag Verma, Sarah A. Pendergrass, Leslie A. Lange, Marylyn D. Ritchie, James G. Wilson, Helena Kuivaniemi, Gerard Tromp, David J. Carey, Glenn S. Gerhard, Murray H. Brilliant, Scott J. Hebbring, Joseph F. Cubells, Julia K. Pinsonneault, Greg J. Norman, Wolfgang Sadee

Abstract

Rationale: Dopamine β-hydroxylase (DBH) catalyzes the conversion of dopamine to norepinephrine in the CNS and peripherally. DBH variants are associated with large changes in circulating DBH and implicated in multiple disorders; yet causal relationships and tissue-specific effects remain unresolved. Objective: To characterize regulatory variants in DBH, effect on mRNA expression, and role in modulating sympathetic tone and disease risk. Methods and Results: Analysis of DBH mRNA in human tissues confirmed high expression in the locus coeruleus (LC) and adrenal gland, but also in sympathetically innervated organs (liver>lung>heart). Allele-specific mRNA assays revealed pronounced allelic expression differences in the liver (2-11-fold) attributable to promoter rs1611115 and exon 2 rs1108580, but only small differences in LC and adrenals. These alleles were also associated with significantly reduced mRNA expression in liver and lung. Although DBH protein is expressed in other sympathetically innervated organs, mRNA levels were too low for analysis. In mice, hepatic Dbh mRNA levels correlated with cardiovascular risk phenotypes. The minor alleles of rs1611115 and rs1108580 were associated with sympathetic phenotypes including angina pectoris. Testing combined effects of these variants suggested protection against myocardial infarction in three separate clinical cohorts. Conclusions: We demonstrate profound effects of DBH variants on expression in two sympathetically innervated organs, liver and lung, but not in adrenals and brain. Preliminary results demonstrate an association of these variants with clinical phenotypes responsive to peripheral sympathetic tone. We hypothesize that in addition to endocrine effects via circulating DBH and norepinephrine, the variants act in sympathetically innervated target organs.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 1 4%
Unknown 22 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 22%
Student > Master 4 17%
Student > Ph. D. Student 4 17%
Student > Bachelor 3 13%
Professor 2 9%
Other 5 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 30%
Agricultural and Biological Sciences 5 22%
Psychology 5 22%
Neuroscience 3 13%
Unspecified 2 9%
Other 1 4%

Attention Score in Context

This research output has an Altmetric Attention Score of 20. 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 10 February 2015.
All research outputs
#634,833
of 11,842,994 outputs
Outputs from Circulation Research
#147
of 5,460 outputs
Outputs of similar age
#17,190
of 259,322 outputs
Outputs of similar age from Circulation Research
#4
of 65 outputs
Altmetric has tracked 11,842,994 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,460 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.2. This one has done particularly well, scoring higher than 97% 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 259,322 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 93% of its contemporaries.
We're also able to compare this research output to 65 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 93% of its contemporaries.