Abstract 17897: Aptamer-Based Proteomic Profiling Identified Novel Markers or Cardiovascular Risk
Background: Emerging proteomic technologies are beginning to permit the systematic characterization of human plasma samples. DNA-aptamer based technologies may address limitations of existing proteomic techniques, including low sample throughput, which have hindered proteomic analyses of large cohorts.
Methods: We applied an aptamer-based proteomic technology that measures 1,129 proteins to identify novel associations between proteins and cardiovascular risk traits [age, sex, total cholesterol, HDL, SBP, diabetes, smoking status and Framingham Risk Score (FRS)] in 899 Framingham Heart Study Exam 5 participants. Age- and sex- adjusted regression analyses were performed for each protein versus clinical trait. Proportional hazards regression models were used for incident cardiovascular disease (CVD) analyses. A Bonferroni-corrected P threshold of 5.54E-06 was used to determine significance.
Results: We found156 proteins associated with the FRS. There were numerous novel relationships with FRS identified, including aminoacylase 1 (β = 0.3386, P = 2.54E-22) and trigger factor 2 (β = 0.2846, P = 5.71E-17). In addition, we identified many novel associations with individual risk traits, including smoking with bone associated osteomodulin (β = -0.8299, P = 4.25E-25) and age with anti-angiogenic factor endostatin (β = 0.2059, P = 2.48E-10). In exploratory age and sex-adjusted analyses, baseline tPA level was associated with future CVD (HR per SD 1.65, P = 2.10E-05). Further, we developed a novel workflow integrating DNA-based immunoaffinity with mass spectrometry to analytically validate aptamer specificity.
Conclusion: This study highlights an emerging proteomics tool capable of profiling > 1,100 low abundance analytes and applicable to large human cohorts. These findings motivate additional biological studies to test for causal relationships as well as clinical studies in large cohorts for validation.
Author Disclosures: D. Ngo: None. S. Sinha: None. D. Shen: None. E. Kuhn: None. M.J. Keyes: None. X. Shi: None. M.D. Benson: None. J.F. O’ Sullivan: None. H. Keshishian: None. L. Farrell: None. R.S. Vasan: None. M.S. Sabatine: None. M.G. Larson: None. S.A. Carr: None. T.J. Wang: None. R.E. Gerszten: None.
- © 2016 by American Heart Association, Inc.