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Identification of novel loci affecting circulating chromogranins and related peptides
- Benyamin, Beben (author)
- Maihofer, Adam X (author)
- Schork, Andrew J (author)
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- Hamilton, Bruce A (author)
- Rao, Fangwen (author)
- Schmid-Schönbein, Geert W (author)
- Zhang, Kuixing (author)
- Mahata, Manjula (author)
- Schork, Nicholas J (author)
- Biswas, Nilima (author)
- Hook, Vivian Y (author)
- Wei, Zhiyun (author)
- Montgomery, Grant W (author)
- Martin, Nicholas G (author)
- Nievergelt, Caroline M (author)
- Whitfield, John B (author)
- O'Connor, Daniel T (author)
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- (creator_code:org_t)
- 2016-12-22
- 2017
- English.
- In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 26:1, s. 233-242
- Journal article (peer-reviewed)
Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
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- Maihofer, Adam X
- Schork, Andrew J
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- Zhang, Kuixing
- Mahata, Manjula
- Stridsberg, Mats
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- Biswas, Nilima
- Hook, Vivian Y
- Wei, Zhiyun
- Montgomery, Gran ...
- Martin, Nicholas ...
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- O'Connor, Daniel ...
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