Inverse changes in plasma tetranectin and titin levels in patients with type 2 diabetes mellitus: a potential predictor of acute myocardial infarction?

Mohd Aizat Abdul RAHIM1, Zubaidah Haji Abdul RAHIM2, Wan Azman WAN AHMAD3, Marina Mohd BAKRI2, Muhammad Dzafir ISMAIL3, Onn Haji HASHIM4,5
1 Centre of Preclinical Science Studies, Faculty of Dentistry, Universiti Teknologi MARA, 47000 Sungai Buloh, Selangor, Malaysia
2 Department of Oral and Craniofacial Sciences, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
3 Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
4 Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
5 University of Malaya Centre for Proteomics Research, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
Correspondence to: Onn Haji HASHIM:,
DOI: 10.1038/aps.2017.141
Received: 7 August 2017
Accepted: 10 October 2017
Advance online: 8 February 2018


An early intervention using biomarkers to predict acute myocardial infarction (AMI) will effectively reduce global heart attack incidence, particularly among high-risk patients with type 2 diabetes mellitus (T2DM). This study attempted to identify potential biomarkers by detecting changes in the levels of plasma proteins in T2DM patients following onset of AMI in comparison with those without AMI. Volunteer T2DM patients without AMI (control; n=10) and T2DM patients with AMI (n=10) were recruited. Plasma samples from these patients were evaluated via two-dimensional gel electrophoresis (2DE) to screen for proteins with level changes between the two groups. The abundance of spots on gel images was analyzed using Progenesis SameSpots and subjected to false discovery rate (FDR) analysis. Protein spots with statistically significant changes of at least 1.5 fold were selected for mass spectrometry (MS) analysis. Due to strong cardiac connections, tetranectin and titin were evaluated by enzymelinked immunosorbent assay (ELISA). The adjusted P-values and fold changes between the two groups resulted in identification of 34 protein spots with significantly altered abundance. Upon MS analysis, 17 plasma proteins were identified: tetranectin, titin, clusterin, haptoglobin, myosin-13, zinc fnger protein 445, DNA repair protein RAD50, serum albumin, apolipoprotein A-IV, caspase-6, aminoacyl tRNA synthase complex-interacting multifunctional protein 1, serotransferrin, retinol-binding protein 4, transthyretin, alpha-1-antitrypsin, apolipoprotein A-I and serum amyloid A. Comparable patterns of changes in tetranectin and titin between the control and AMI groups were confirmed using ELISA. In summary, tetranectin and titin in plasma appeared to be closely associated with the onset of AMI among T2DM patients and can be used as potential biomarkers for prediction of a cardiac event, though this requires validation in a prospective cohort study.
Keywords: tetranectin; titin; acute myocardial infarction; coronary disease; diabetes mellitus; proteomics; 2D gel electrophoresis; enzyme-linked immunosorbent assay

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