A novel troponin T peptide in humans: Assay, biochemistry and preliminary findings in acute coronary syndromes.
BACKGROUND
High sensitivity assays for cardiac troponin (cTn) have reduced time to diagnosis of myocardial infarction (MI) but at costs to diagnostic specificity. We hypothesised that measurement of an upstream open reading frame peptide (uORF) from the human cTnT gene (TnTuORF) might improve cTn specificity in MI patients.


METHODS
A novel immunoassay to TnTuORF was developed and used to document circulating concentrations in normal healthy volunteers (n=150); assess potential trans-organ secretion in patients undergoing cardiac catheterisation (n=16); characterise temporal TnTuORF concentrations during ST-elevation MI (STEMI, n=4) and assess the potential of TnTuORF to assist the diagnosis and prognosis of MI in patients presenting with chest pain suspicious of ACS (n=502). Plasma immunoreactive TnTuORF was characterised on reverse phase and size exclusion HPLC.


RESULTS
In normal volunteers and suspected acute coronary syndrome (ACS) patients, TnTuORF had no relationship with TnI or TnT. Trans-organ venous sampling suggested TnTuORF secretion is not exclusively cardiac based. In STEMI patients, TnTuORF concentrations decreased for up to 12h after onset. In suspected ACS patients, TnTuORF could not diagnose MI (ROC AUC=0.446, P=0.117) but could diagnose cardiac disorders other than MI (AUC=0.79, P<0.001).


CONCLUSIONS
This is the first evidence for a circulating uORF peptide. TnTuORF does not appear to aid the diagnosis of MI but further studies to assess its potential in cardiovascular disease are required.
Christchurch Heart Institute, University of Otago, 2 Riccarton Avenue, Christchurch 8011, New Zealand.
J
J
Lee
Christchurch Heart Institute, University of Otago, 2 Riccarton Avenue, Christchurch 8011, New Zealand.
J
J
Young
Department of Medicine, University of Otago, Christchurch 8011, New Zealand.
C M
CM
Frampton
Christchurch Hospital, New Zealand.
S
S
Aldous
Christchurch Heart Institute, University of Otago, 2 Riccarton Avenue, Christchurch 8011, New Zealand.
R W
RW
Troughton
Christchurch Hospital, New Zealand.
M
M
Than
Christchurch Heart Institute, University of Otago, 2 Riccarton Avenue, Christchurch 8011, New Zealand.
A M
AM
Richards
Christchurch Heart Institute, University of Otago, 2 Riccarton Avenue, Christchurch 8011, New Zealand. Electronic address: chris.pemberton@otago.ac.nz.
C J
CJ
Pemberton
D054058:Acute Coronary Syndrome / Q000097:blood* / Q000175:diagnosis*; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008297:Male; D008875:Middle Aged; D016366:Open Reading Frames / Q000502:physiology*; D010446:Peptide Fragments / Q000097:blood* / Q000235:genetics; D011446:Prospective Studies; D020107:Troponin T / Q000097:blood* / Q000235:genetics
D015415:Biomarkers; D010446:Peptide Fragments; D020107:Troponin T
Biomarkers; Myocardial infarction; Troponin; Upstream open reading frame