期刊
JOURNAL OF INTERNAL MEDICINE
卷 290, 期 4, 页码 855-865出版社
WILEY
DOI: 10.1111/joim.13327
关键词
apoptosis; atherosclerosis; biomarker; diabetes
资金
- Swedish Society for Medical Research [AE S16-0100]
- Emil and Wera Cornell Foundation
- Swedish Research Council [AE 2019-01907, MO-M 2018-02784, OM 2018-02760, GE 2019-01236]
- Crafoord Foundation [AE 20190864]
- Swedish Society of Medicine [AE SLS-880161]
- Swedish Heart and Lung Foundation [MO-M 20200711, OM 20180278, GE 20200173, AE 20200504]
- Southern Sweden Regional Research Funding
- Ake Wiberg Foundation [AE M19-0524]
- Novo Nordic Foundation [NNF20OC0063886]
- Knut and Alice Wallenberg Foundation
- Medical Faculty at Lund University
- Region Skane
- Lund University Diabetes Center (Exodiab-Swedish Research Council) [Dnr 2009-1039]
- Lund University Diabetes Center (LUDC-IRC Swedish Foundation for Strategic Research) [Dnr IRC15-0067]
- SUS foundations
- Swedish Research Council [2019-01907] Funding Source: Swedish Research Council
Plasma sCaspase-3 is strongly associated with HbA1c and predicts future risk of diabetes and CAD, making it a potential marker for cardio-metabolic risk factors.
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 Malmo 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 x 10(-5)) and CAD (HR 1.2 per 1 unit, P = 1 x 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 x 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.
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