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Identification of novel loci affecting circulating chromogranins and related peptides
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2017 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 26, no 1, p. 233-242Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2017. Vol. 26, no 1, p. 233-242
National Category
Clinical Laboratory Medicine
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URN: urn:nbn:se:uu:diva-318357DOI: 10.1093/hmg/ddw380ISI: 000397064600019PubMedID: 28011710OAI: oai:DiVA.org:uu-318357DiVA, id: diva2:1084382
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NIH (National Institute of Health), P01HL058120-10 R01MH093500Available from: 2017-03-24 Created: 2017-03-24 Last updated: 2017-11-29Bibliographically approved

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Stridsberg, Mats

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