A haplotype of angiotensinogen gene that is associated with essential hypertension increases its promoter activity in adipocytes

Vascul Pharmacol. 2006 Jan;44(1):29-33. doi: 10.1016/j.vph.2005.09.009. Epub 2005 Nov 21.

Abstract

Obesity is associated with hypertension and other cardiovascular diseases especially in the African-American population. Human angiotensinogen (AGT) gene has seven single nucleotide polymorphisms (SNPs) in 1.2 kb region of its promoter. Recent studies have shown that variant -217A is associated with hypertension in African-American and Chinese population. Nucleotide sequence of the hAGT gene has shown that variant -217A almost always occurs with variants -532T, -793A and -1074T (forming haplotype AAT) and variant -217G almost always occurs with variants -532C, -793G and -1074G (forming haplotype GGG). Since hAGT gene is expressed in the adipose tissue and its expression in this tissue may play a role in hypertension, we have analyzed the role of haplotypes AAT and GGG on the expression of this gene in adipocytes. We show here that a reporter construct with haplotype AAT of the hAGT gene has increased promoter activity on transient transfection in pre-adipocytes and differentiated adipocytes as compared to the reporter construct containing GCGG haplotype. Increased expression of the AGT gene containing haplotype AAT in the liver and adipocytes may be a contributing factor for hypertension.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Angiotensinogen / genetics*
  • Animals
  • Dexamethasone / pharmacology
  • Haplotypes
  • Humans
  • Hypertension / genetics*
  • Mice
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic* / drug effects
  • Recombinant Fusion Proteins / biosynthesis
  • Transcription, Genetic
  • Transfection

Substances

  • Recombinant Fusion Proteins
  • Angiotensinogen
  • Dexamethasone