Identification of novel loci affecting circulating chromogranins and related peptides

Benyamin, Beben, Maihofer, Adam X., Schork, Andrew J., Hamilton, Bruce A., Rao, Fangwen, Schmid-Schonbein, Geert W., Zhang, Kuixing, Mahata, Manjula, Stridsberg, Mats, Schork, Nicholas J., Biswas, Nilima, Hook, Vivian Y., Wei, Zhiyun, Montgomery, Grant W., Martin, Nicholas G., Nievergelt, Caroline M., Whitfield, John B. and O'Connor, Daniel T. (2017) Identification of novel loci affecting circulating chromogranins and related peptides. Human Molecular Genetics, 26 1: 233-242. doi:10.1093/hmg/ddw380

Author Benyamin, Beben
Maihofer, Adam X.
Schork, Andrew J.
Hamilton, Bruce A.
Rao, Fangwen
Schmid-Schonbein, Geert W.
Zhang, Kuixing
Mahata, Manjula
Stridsberg, Mats
Schork, Nicholas J.
Biswas, Nilima
Hook, Vivian Y.
Wei, Zhiyun
Montgomery, Grant W.
Martin, Nicholas G.
Nievergelt, Caroline M.
Whitfield, John B.
O'Connor, Daniel T.
Title Identification of novel loci affecting circulating chromogranins and related peptides
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
Publication date 2017-01-01
Year available 2016
Sub-type Article (original research)
DOI 10.1093/hmg/ddw380
Open Access Status Not yet assessed
Volume 26
Issue 1
Start page 233
End page 242
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2017
Language eng
Formatted abstract
Chromogranins are pro-hormone secretory proteins released from neuroendocrine cells, with effects on control of blood pressure. We conducted a genome-wide association study for plasma catestatin, the catecholamine release inhibitory peptide derived from chromogranin A (CHGA), and other CHGA- or chromogranin B (CHGB)-related peptides, in 545 US and 1252 Australian subjects. This identified loci on chromosomes 4q35 and 5q34 affecting catestatin concentration (P = 3.40 × 10−30 for rs4253311 and 1.85 × 10−19 for rs2731672, respectively). Genes in these regions include the proteolytic enzymes kallikrein (KLKB1) and Factor XII (F12). In chromaffin cells, CHGA and KLKB1 proteins co-localized in catecholamine storage granules. In vitro, kallikrein cleaved recombinant human CHGA to catestatin, verified by mass spectrometry. The peptide identified from this digestion (CHGA360–373) selectively inhibited nicotinic cholinergic stimulated catecholamine release from chromaffin cells. A proteolytic cascade involving kallikrein and Factor XII cleaves chromogranins to active compounds both in vivo and in vitro.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
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