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Identification of novel loci affecting circulating chromogranins and related peptides.
Benyamin, Beben; Maihofer, Adam X; Schork, Andrew J; Hamilton, Bruce A; Rao, Fangwen; Schmid-Schönbein, 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.
Afiliação
  • Benyamin B; Institute for Molecular Bioscience, University of Queensland, Australia.
  • Maihofer AX; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Schork AJ; Department of Psychiatry.
  • Hamilton BA; Cognitive Science.
  • Rao F; Medicine.
  • Schmid-Schönbein GW; Medicine.
  • Zhang K; Bioengineering.
  • Mahata M; Medicine.
  • Stridsberg M; Medicine.
  • Schork NJ; University of California at San Diego, La Jolla, CA.
  • Biswas N; Department of Medical Sciences, Uppsala University, Sweden and.
  • Hook VY; J Craig Venter Institute, La Jolla, CA, USA.
  • Wei Z; Medicine.
  • Montgomery GW; Medicine.
  • Martin NG; Medicine.
  • Nievergelt CM; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Whitfield JB; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • O'Connor DT; Department of Psychiatry.
Hum Mol Genet ; 26(1): 233-242, 2017 01 01.
Article em En | MEDLINE | ID: mdl-28011710
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fragmentos de Peptídeos / Biomarcadores / Catecolaminas / Células Cromafins / Cromogranina A / Loci Gênicos / Hipertensão Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Adolescent / Adult / Aged / Animals / Female / Humans / Male / Middle aged País como assunto: America do norte / Oceania Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fragmentos de Peptídeos / Biomarcadores / Catecolaminas / Células Cromafins / Cromogranina A / Loci Gênicos / Hipertensão Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Adolescent / Adult / Aged / Animals / Female / Humans / Male / Middle aged País como assunto: America do norte / Oceania Idioma: En Ano de publicação: 2017 Tipo de documento: Article