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| PMID |
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| TITLE |
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| Identification of Novel Loci Affecting Circulating Chromogranins and Related Peptides. |
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| ABSTRACT |
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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. |
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| DATE PUBLISHED |
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| HISTORY |
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| 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 |
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| AUTHORS |
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| 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 |
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(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 |
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(2) QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
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(2) QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
| Nievergelt CM |
|
Nievergelt |
Caroline M |
CM |
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(3) Departments of Psychiatry, University of California at San Diego, La Jolla, CA. |
| Whitfield JB |
|
Whitfield |
John B |
JB |
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(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. |
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| INVESTIGATORS |
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| JOURNAL |
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| 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 |
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| MEDLINE JOURNAL |
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| MEDLINETA: Hum Mol Genet |
| COUNTRY: England |
| ISSNLINKING: 0964-6906 |
| NLMUNIQUEID: 9208958 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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