Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
28011710
TITLE
Identification of Novel Loci Affecting Circulating Chromogranins and Related Peptides.
ABSTRACT
NlmCategory: UNASSIGNED
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 x 10(-30) for rs4253311 and 1.85 x 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.
The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
DATE PUBLISHED
2016 Dec 22
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2016/07/28
revised 2016/10/17
accepted 2016/11/02
pubmed 2016/12/25 06:00
medline 2016/12/25 06:00
entrez 2016/12/25 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Benyamin B Benyamin Beben B (2) QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Maihofer AX Maihofer Adam X AX (3) Departments of Psychiatry, University of California at San Diego, La Jolla, CA.
Schork AJ Schork Andrew J AJ (4) Departments of Cognitive Science, University of California at San Diego, La Jolla, CA.
Hamilton BA Hamilton Bruce A BA (5) Departments of Medicine, University of California at San Diego, La Jolla, CA.
Rao F Rao Fangwen F (5) Departments of Medicine, University of California at San Diego, La Jolla, CA.
Schmid-SchÖnbein GW Schmid-SchÖnbein Geert W GW (6) Departments of Bioengineering, University of California at San Diego, La Jolla, CA.
Zhang K Zhang Kuixing K (5) Departments of Medicine, University of California at San Diego, La Jolla, CA.
Mahata M Mahata Manjula M (5) Departments of Medicine, University of California at San Diego, La Jolla, CA.
Stridsberg M Stridsberg Mats M (7) Department of Medical Sciences, Uppsala University, Sweden.
Schork NJ Schork Nicholas J NJ (8) J Craig Venter Institute, La Jolla, CA.
Biswas N Biswas Nilima N (5) Departments of Medicine, University of California at San Diego, La Jolla, CA.
Hook VY Hook Vivian Y VY (5) Departments of Medicine, University of California at San Diego, La Jolla, CA.
Wei Z Wei Zhiyun Z (5) Departments of Medicine, University of California at San Diego, La Jolla, CA.
Montgomery GW Montgomery Grant W GW (2) QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Martin NG Martin Nicholas G NG (2) QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Nievergelt CM Nievergelt Caroline M CM (3) Departments of Psychiatry, University of California at San Diego, La Jolla, CA.
Whitfield JB Whitfield John B JB (2) QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia John.Whitfield@qimrberghofer.edu.au.
O'Connor DT O'Connor Daniel T DT (5) Departments of Medicine, University of California at San Diego, La Jolla, CA.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Human molecular genetics
ISOABBREVIATION: Hum. Mol. Genet.
YEAR: 2016
MONTH: Dec
DAY: 22
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1460-2083
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Hum Mol Genet
COUNTRY: England
ISSNLINKING: 0964-6906
NLMUNIQUEID: 9208958
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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