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Pratibha Singh

Assistant researcher

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Hyperglycaemia-associated Caspase-3 predicts diabetes and coronary artery disease events

Author

  • Jiangming Sun
  • Pratibha Singh
  • Johan Österlund
  • Marju Orho-Melander
  • Olle Melander
  • Gunnar Engström
  • Andreas Edsfeldt

Summary, in English

BACKGROUND: Apoptosis is central in both diabetes and atherosclerosis, linked to pancreatic beta cell death and plaque progression. Circulating Caspase-3 has also been associated with diabetes and coronary calcium score. Here, we explored if soluble Caspase-3 (sCaspase-3) is associated with cardio-metabolic risk factors and predicts incidence of diabetes and coronary artery disease (CAD).

METHODS: Clinical data and plasma from 4637 individuals from the Malmö Diet and Cancer cohort were studied. Plasma sCaspase-3 was measured by a Proximity Extension Assay. National registers were used to identify diabetes and CAD events during follow-up. Type 2 diabetes risk variants and expression quantitative trait loci (eQTL) for sCaspase-3 were retrieved from the DIAGRAM consortium and the Genotype-Tissue Expression project.

RESULTS: HbA1c was the factor with the strongest association with sCaspase-3 (r = 0.18, P = 1.3x10-36 ). During follow-up 666 individuals developed diabetes and 648 individuals suffered from CAD. Increasing sCaspase-3 was associated with a higher risk of developing diabetes (hazard ratio (HR) 1.18 per 1unit; P = 7 × 10-5 ) and CAD (HR 1.2 per 1 unit, P = 1 × 10-4 ) during follow-up. A genetic variant rs60780116, located upstream of CASP3, showed strong association with type 2 diabetes (OR 1.06, 95%CI 1.04-1.07, P = 8.4 × 10-11 ). An eQTL was identified between this variant and gene expression of CASP3, where the allele positively correlated with type 2 diabetes was associated with increased CASP3 expression in blood.

CONCLUSIONS: The present study provides evidence for plasma sCaspase-3 as a marker of cardio-metabolic risk factors and as a predictor of future diabetes and CAD in a cohort without cardiovascular disease or diabetes at baseline.

Department/s

  • Cardiovascular Research - Translational Studies
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Diabetes - Molecular Metabolism
  • Diabetes - Cardiovascular Disease
  • EpiHealth: Epidemiology for Health
  • Cardiovascular Research - Hypertension
  • Cardiovascular Research - Epidemiology
  • WCMM-Wallenberg Centre for Molecular Medicine

Publishing year

2021

Language

English

Pages

855-865

Publication/Series

Journal of Internal Medicine

Volume

290

Issue

4

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Endocrinology and Diabetes
  • Cardiac and Cardiovascular Systems

Status

Published

Project

  • MOVING FROM BIOMARKERS TO MECHANISM ORIENTED PREVENTION OF CARDIOMETABOLIC DISEASE

Research group

  • Cardiovascular Research - Translational Studies
  • Diabetes - Molecular Metabolism
  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Hypertension
  • Cardiovascular Research - Epidemiology

ISBN/ISSN/Other

  • ISSN: 1365-2796