Both rare and common polymorphisms contribute functional variation at CHGA, a regulator of catecholamine physiology

Am J Hum Genet. 2004 Feb;74(2):197-207. doi: 10.1086/381399. Epub 2004 Jan 12.


The chromogranin/secretogranin proteins are costored and coreleased with catecholamines from secretory vesicles in chromaffin cells and noradrenergic neurons. Chromogranin A (CHGA) regulates catecholamine storage and release through intracellular (vesiculogenic) and extracellular (catecholamine release-inhibitory) mechanisms. CHGA is a candidate gene for autonomic dysfunction syndromes, including intermediate phenotypes that contribute to human hypertension. Here, we show a surprising pattern of CHGA variants that alter the expression and function of this gene, both in vivo and in vitro. Functional variants include both common alleles that quantitatively alter gene expression and rare alleles that qualitatively change the encoded product to alter the signaling potency of CHGA-derived catecholamine release-inhibitory catestatin peptides.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Catecholamines / physiology*
  • Chromogranin A
  • Chromogranins / genetics*
  • Humans
  • Molecular Sequence Data
  • PC12 Cells
  • Phylogeny
  • Polymorphism, Genetic*
  • Rats
  • Spectrometry, Mass, Electrospray Ionization


  • Catecholamines
  • Chromogranin A
  • Chromogranins