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Cited by 15Renin-Angiotensin System StudiesGenetic Associations and EpidemiologyGenomics and Chromatin Dynamics

Allele-Specific Expression of Angiotensinogen in Human Subcutaneous Adipose Tissue

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Park, Sungmi, Lu, Ko-Ting, Liu, Xuebo, Chatterjee, Tapan K., Rudich, Steven M., Weintraub, Neal L., Kwitek, Anne E., Sigmund, Curt D.·2013·Hypertension
DOI 10.1161/hypertensionaha.113.01330PMC PMC3718031
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Abstract

The angiotensinogen gene is genetically linked with hypertension, but the mechanistic basis for association of sequence variants in the promoter and coding region of the gene remains unclear. An E-box at position −20 has been hypothesized to control the level of angiotensinogen expression, but its mechanistic importance for angiotensinogen expression in human tissues is uncertain. We developed an allele-specific polymerase chain reaction–based assay to distinguish between angiotensinogen mRNA derived from variants at the −20 position (rs5050) in the angiotensinogen promoter in adipose tissues obtained during surgery. The assay takes advantage of linkage disequilibrium between the rs5050 (located in the promoter) and rs4762 (located in the coding region) single nucleotide polymorphisms. This strategy allowed us to assess the level of allele-specific expression in A-20C heterozygous subjects comparing the relative proportion of each allele with the total, thus eliminating the problem of variability in the level of total angiotensinogen mRNA among subjects. We show that angiotensinogen mRNA derived from the −20C allele is expressed significantly higher than that derived from the −20A allele in subcutaneous adipose tissue, and increased expression correlates with enriched chromatin binding of upstream stimulatory factor-2 to the −20C E-box compared with −20A. This may be depot selective because we were unable to detect these differences in omental adipose. This provides the first data directly comparing expression of angiotensinogen mRNA and differential transcription factor binding derived from 2 variant alleles in human tissue where the ratio of expression of one allele to another can be accurately determined

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  • This analysis showed enhanced levels in the subcutaneous adipose tissue of the mRNA derived from a particular allele of the angiotensinogen gene bearing the −20C variant in its promoter.

    “This analysis also showed enhanced levels in the subcutaneous adipose tissue of the mRNA derived from a particular allele of the angiotensinogen gene bearing the −20C variant in its promoter.”

    From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [59]

  • This was associated with enriched binding to the −20C allele of a transcription factor, the upstream stimulatory factor 2, which is essential for angiotensinogen transcriptional regulation.

    “This was associated with enriched binding to the −20C allele of a transcription factor, the upstream stimulatory factor 2, which is essential for angiotensinogen transcriptional regulation (59).”

    From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [59]

  • Analysis of human adipose tissues obtained during surgery revealed a great variability in the total level of angiotensinogen gene expression among subjects.

    “Analysis of human adipose tissues obtained during surgery revealed a great variability in the total level of angiotensinogen gene expression among subjects (59).”

    From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [59]

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Authors
Park, S., Lu, K.-T., Liu, X., Chatterjee, T. K., Rudich, S. M., Weintraub, N. L., Kwitek, A. E., & Sigmund, C. D.
Affiliations
University of Iowa (US)
ORCID
Venue
Hypertension
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2013-07
Volume
62
Issue
1
Pages
41-47
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
DOI
10.1161/hypertensionaha.113.01330
PMC
PMC3718031
OpenAlex
W2115524332
Cited by
15
References
38
Citations by year
2025: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 1 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 1 · 2013: 1
FWCI
1.58
Type
journal article
Language
en
Open access
Locations
  • Hypertension (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL048058, R01HL089895, P01HL062984, R01HL061446, HL-062984, HL048058, R01HL112640, R37HL048058, R01HL076684, HL-084207, HL089895, HL112640, P01HL084207, HL061446, HL-076684)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R21DK089417, DK089417)
  • National Institute of Environmental Health Sciences (P30ES005605)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
angiotensinogen, allele-specific expression, subcutaneous adipose tissue, E-box, promoter polymorphism, linkage disequilibrium, transcription factor binding, omental adipose tissue, single nucleotide polymorphisms
MeSH terms
Adult, Alleles, Angiotensinogen, Female, Gene Expression Regulation, Humans, Male, Obesity, Promoter Regions, Genetic, RNA, Messenger, Linkage Disequilibrium, Genetic Predisposition to Disease, Subcutaneous Fat

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