title: Both rare and common polymorphisms contribute functional variation at CHGA, a regulator of catecholamine physiology.
abstract: 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.
authors.affiliation: Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.
authors.forename: Gen
authors.initials: G
authors.lastname: Wen
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Mahata
authors.forename: Peter
authors.initials: P
authors.lastname: Cadman
authors.forename: Manjula
authors.initials: M
authors.lastname: Mahata
authors.forename: Sajalendu
authors.initials: S
authors.lastname: Ghosh
authors.forename: Nitish R
authors.initials: NR
authors.lastname: Mahapatra
authors.forename: Fangwen
authors.initials: F
authors.lastname: Rao
authors.forename: Mats
authors.initials: M
authors.lastname: Stridsberg
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Smith
authors.forename: Payam
authors.initials: P
authors.lastname: Mahboubi
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
authors.forename: Daniel T
authors.initials: DT
authors.lastname: O'Connor
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Hamilton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002395:Catecholamines / Q000502:physiology*; D053379:Chromogranin A; D002864:Chromogranins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D016716:PC12 Cells; D010802:Phylogeny; D011110:Polymorphism, Genetic; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D002395:Catecholamines; D053379:Chromogranin A; D002864:Chromogranins