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Promoter polymorphisms in ace (angiotensin i-converting enzyme) associated with clinical outcomes in hypertension

Academic Article
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Overview

authors

  • Johnson, A. D.
  • Gong, Y.
  • Wang, D.
  • Langaee, T. Y.
  • Shin, J.
  • Cooper-DeHoff, R. M.
  • Schork, Nicholas
  • Binkley, P.
  • Pepine, C. J.
  • Johnson, J. A.
  • Sadee, W.

publication date

  • January 2009

journal

  • Clinical Pharmacology & Therapeutics  Journal

abstract

  • Genetic variants of ACE are suspected risk factors in cardiovascular disease, but the alleles responsible for the variations remain unidentified. To search for regulatory polymorphisms, allelic angiotensin I-converting enzyme (ACE) mRNA expression was measured in 65 heart tissues, followed by genotype scanning of the ACE locus. Marked allelic expression imbalance (AEI) detected in five African-American subjects was associated with single-nucleotide polymorphisms (SNPs) (rs7213516, rs7214530, and rs4290) residing in conserved regions 2-3 kb upstream of ACE. Moreover, each of the SNPs affected transcription in reporter gene assays. SNPs rs4290 and rs7213516 were tested for associations with adverse cardiovascular outcomes in hypertensive patients with coronary disease (International Verapamil SR Trandolapril Study Genetic Substudy (INVEST-GENES), n = 1,032). Both SNPs were associated with adverse cardiovascular outcomes, largely attributable to nonfatal myocardial infarction in African Americans, showing an odds ratio of 6.16 (2.43-15.60) (P < 0.0001) for rs7213516. The high allele frequency in African Americans (16%) compared to Hispanics (4%) and Caucasians (<1%) suggests that these alleles contribute to variation between populations in cardiovascular risk and treatment outcomes.

subject areas

  • African Americans
  • Aged
  • Antihypertensive Agents
  • Case-Control Studies
  • Coronary Disease
  • Ethnic Groups
  • Female
  • Genes, Reporter
  • Genetic Variation
  • Humans
  • Hypertension
  • Male
  • Peptidyl-Dipeptidase A
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
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Identity

PubMed Central ID

  • PMC2709290

International Standard Serial Number (ISSN)

  • 0009-9236

Digital Object Identifier (DOI)

  • 10.1038/clpt.2008.194

PubMed ID

  • 18946466
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Additional Document Info

start page

  • 36

end page

  • 44

volume

  • 85

issue

  • 1

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