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Elhadad, M.A. ; Gomez Alonso, M.D.C. ; Chen, C.-W- ; Neumeyer, S. ; Delerue, T. ; Rathmann, W.* ; Näbauer, M.* ; Meisinger, C.* ; Kääb, S.* ; Seissler, J.* ; Graumann, J.* ; Koenig, W.* ; Suhre, K.* ; Gieger, C. ; Völker, U.* ; Peters, A. ; Hammer, E.* ; Waldenberger, M.

Plasma proteome association with coronary heart disease and carotid intima media thickness: Results from the KORA F4 study.

Cardiovasc. Diabetol. 23:181 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND AND AIMS: Atherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with CHD and with carotid intima-media thickness (CIMT), as a surrogate measure of atherosclerosis. METHODS: The discovery phase included 1000 participants from the KORA F4 study, whose plasma protein levels were quantified using the aptamer-based SOMAscan proteomics platform. We evaluated the associations of plasma protein levels with CHD using logistic regression, and with CIMT using linear regression. For both outcomes we applied two models: an age-sex adjusted model, and a model additionally adjusted for body mass index, smoking status, physical activity, diabetes status, hypertension status, low density lipoprotein, high density lipoprotein, and triglyceride levels (fully-adjusted model). The replication phase included a matched case-control sample from the independent KORA F3 study, using ELISA-based measurements of galectin-4. Pathway analysis was performed with nominally associated proteins (p-value < 0.05) from the fully-adjusted model. RESULTS: In the KORA F4 sample, after Bonferroni correction, we found CHD to be associated with five proteins using the age-sex adjusted model: galectin-4 (LGALS4), renin (REN), cathepsin H (CTSH), and coagulation factors X and Xa (F10). The fully-adjusted model yielded only the positive association of galectin-4 (OR = 1.58, 95% CI = 1.30-1.93), which was successfully replicated in the KORA F3 sample (OR = 1.40, 95% CI = 1.09-1.88). For CIMT, we found four proteins to be associated using the age-sex adjusted model namely: cytoplasmic protein NCK1 (NCK1), insulin-like growth factor-binding protein 2 (IGFBP2), growth hormone receptor (GHR), and GDNF family receptor alpha-1 (GFRA1). After assessing the fully-adjusted model, only NCK1 remained significant (β = 0.017, p-value = 1.39e-06). Upstream regulators of galectin-4 and NCK1 identified from pathway analysis were predicted to be involved in inflammation pathways. CONCLUSIONS: Our proteome-wide association study identified galectin-4 to be associated with CHD and NCK1 to be associated with CIMT. Inflammatory pathways underlying the identified associations highlight the importance of inflammation in the development and progression of CHD.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Atherosclerosis ; Cardiovascular Disease ; Carotid Intima Media Thickness ; Coronary Artery Disease ; Galectin-4 ; Nck1 ; Proteomics ; Stroke; Cardiovascular Events; Myocardial-infarction; Risk; Biomarkers; Prediction; Relevance; Reveals; Plaque
ISSN (print) / ISBN 1475-2840
e-ISSN 1475-2840
Zeitschrift Cardiovascular Diabetology
Quellenangaben Band: 23, Heft: 1, Seiten: , Artikelnummer: 181 Supplement: ,
Verlag BioMed Central
Verlagsort Campus, 4 Crinan St, London N1 9xw, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology II (EPI2)
Förderungen Bavarian State Ministry of Health and Care through the research project DigiMed Bayern
German Centre for Cardiovascular Research (DZHK)
Ludwig-Maximilians-Universitat, as part of LMUinnovativ
KORA within the Munich Center of Health Sciences (MC Health)
State of Bavaria
Helmholtz Zentrum Munchen- German Research Center for Environmental Health - German Federal Ministry of Education and Research (BMBF)
Projekt DEAL