title: Biomarker discovery by plasma proteomics in familial Brugada Syndrome.
abstract: Brugada Syndrome (BS) is a polygenic inherited cardiac disease characterized by life-threatening arrhythmias and high incidence of sudden death. In this study, two-dimensional gel electrophoresis (2D-PAGE) coupled to mass spectrometry (LC-MS/MS) was used to investigate specific changes in the plasma proteome of BS patients and family members sharing the same gene mutation (SCN5AQ1118X), with the aim to identify novel disease biomarkers. Our data demonstrate that the levels of several proteins were significantly altered in BS patients compared with controls. In particular, apolipoprotein E, prothrombin, vitronectin, complement-factor H, vitamin-D-binding protein, voltage-dependent anion-selective channel protein 3 and clusterin were considerably increased in plasma sample of BS patients, whereas alpha-1-antitrypsin, fibrinogen and angiotensinogen were considerably decreased; moreover, post-translational modifications of antithrombin-III were detected in all affected individuals. On the light of these results, we hypothesize that these proteins might be considered as potential markers for the identification of disease status in BS.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Magna Graecia, Germaneto University Campus, 88100 Catanzaro, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Di Domenico
authors.forename: D
authors.initials: D
authors.lastname: Scumaci
authors.forename: S
authors.initials: S
authors.lastname: Grasso
authors.forename: M
authors.initials: M
authors.lastname: Gaspari
authors.forename: A
authors.initials: A
authors.lastname: Curcio
authors.forename: A
authors.initials: A
authors.lastname: Oliva
authors.forename: F
authors.initials: F
authors.lastname: Ausania
authors.forename: C
authors.initials: C
authors.lastname: Di Nunzio
authors.forename: C
authors.initials: C
authors.lastname: Ricciardi
authors.forename: A C
authors.initials: AC
authors.lastname: Santini
authors.forename: F A
authors.initials: FA
authors.lastname: Rizzo
authors.forename: C
authors.initials: C
authors.lastname: Romano Carratelli
authors.forename: M
authors.initials: M
authors.lastname: Lamberti
authors.forename: D
authors.initials: D
authors.lastname: Conti
authors.forename: R
authors.initials: R
authors.lastname: La Montagna
authors.forename: V
authors.initials: V
authors.lastname: Tomei
authors.forename: V
authors.initials: V
authors.lastname: Malafoglia
authors.forename: V L
authors.initials: VL
authors.lastname: Pascali
authors.forename: P
authors.initials: P
authors.lastname: Ricci
authors.forename: C
authors.initials: C
authors.lastname: Indolfi
authors.forename: F
authors.initials: F
authors.lastname: Costanzo
authors.forename: G
authors.initials: G
authors.lastname: Cuda
mesh_terms: D000990:Antithrombin III / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000097:blood*; D053840:Brugada Syndrome / Q000097:blood / Q000235:genetics*; D004562:Electrocardiography; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008297:Male; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics; D010375:Pedigree; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D011516:Prothrombin / Q000235:genetics; D053719:Tandem Mass Spectrometry; D000515:alpha 1-Antitrypsin / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D062554:NAV1.5 Voltage-Gated Sodium Channel; D020543:Proteome; C568320:SCN5A protein, human; C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin; D000990:Antithrombin III; D011516:Prothrombin