Deciphering the Plasma Proteome of Type 2 Diabetes

Elhadad, Mohamed A.; Jonasson, Christian; Huth, Cornelia; Wilson, Rory; Gieger, Christian; Matias, Pamela; Grallert, Harald; Graumann, Johannes; Gailus-Durner, Valerie; Rathmann, Wolfgang; Toerne, Christine von; Hauck, Stefanie M.; König, Wolfgang; Sinner, Moritz F.; Oprea, Tudor I.; Suhre, Karsten ; Thorand, Barbara; Hveem, Kristian; Peters, Annette und Waldenberger, Melanie (2020): Deciphering the Plasma Proteome of Type 2 Diabetes. In: Diabetes, Bd. 69, Nr. 12: S. 2766-2778

Abstract

With an estimated prevalence of 463 million affected, type 2 diabetes represents a major challenge to health care systems worldwide. Analyzing the plasma proteomes of individuals with type 2 diabetes may illuminate hitherto unknown functional mechanisms underlying disease pathology. We assessed the associations between type 2 diabetes and >1,000 plasma proteins in the Cooperative Health Research in the Region of Augsburg (KORA) F4 cohort (n = 993, 110 cases), with subsequent replication in the third wave of the Nord-Trondelag Health Study (HUNT3) cohort (n = 940, 149 cases). We computed logistic regression models adjusted for age, sex, BMI, smoking status, and hypertension. Additionally, we investigated associations with incident type 2 diabetes and performed two-sample bidirectional Mendelian randomization (MR) analysis to prioritize our results. Association analysis of prevalent type 2 diabetes revealed 24 replicated proteins, of which 8 are novel. Proteins showing association with incident type 2 diabetes were aminoacylase-1, growth hormone receptor, and insulin-like growth factor-binding protein 2. Aminoacylase-1 was associated with both prevalent and incident type 2 diabetes. MR analysis yielded nominally significant causal effects of type 2 diabetes on cathepsin Z and rennin, both known to have roles in the pathophysiological pathways of cardiovascular disease, and of sex hormone-binding globulin on type 2 diabetes. In conclusion, our high-throughput proteomics study replicated previously reported type 2 diabetes-protein associations and identified new candidate proteins possibly involved in the pathogenesis of type 2 diabetes.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0012-1797
• Sprache: Englisch