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- Title
Hyperglycaemia-associated Caspase-3 predicts diabetes and coronary artery disease events.
- Authors
Sun, Jiangming; Singh, Pratibha; Österlund, Johan; Orho‐Melander, Marju; Melander, Olle; Engström, Gunnar; Edsfeldt, Andreas; Orho-Melander, Marju
- Abstract
<bold>Background: </bold>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).<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
CORONARY artery disease; DIABETES; CASPASES; TYPE 2 diabetes; ATHEROSCLEROSIS; CARDIOVASCULAR diseases; PANCREATIC beta cells
- Publication
Journal of Internal Medicine, 2021, Vol 290, Issue 4, p855
- ISSN
0954-6820
- Publication type
journal article
- DOI
10.1111/joim.13327