Details

Autor(en) / Beteiligte

• Naber, Annemieke
• Demus, Daniel
• Slieker, Roderick C
• Nicolardi, Simone
• Beulens, Joline W J
• Elders, Petra J M
• Lieverse, Aloysius G
• Sijbrands, Eric J G
• 't Hart, Leen M
• Wuhrer, Manfred
• van Hoek, Mandy

Titel

Apolipoprotein-CIII O-Glycosylation Is Associated with Micro- and Macrovascular Complications of Type 2 Diabetes

Ist Teil von

• International journal of molecular sciences, 2024-05, Vol.25 (10), p.5365

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2024

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Apolipoprotein-CIII (apo-CIII) inhibits the clearance of triglycerides from circulation and is associated with an increased risk of diabetes complications. It exists in four main proteoforms: O-glycosylated variants containing either zero, one, or two sialic acids and a non-glycosylated variant. O-glycosylation may affect the metabolic functions of apo-CIII. We investigated the associations of apo-CIII glycosylation in blood plasma, measured by mass spectrometry of the intact protein, and genetic variants with micro- and macrovascular complications (retinopathy, nephropathy, neuropathy, cardiovascular disease) of type 2 diabetes in a DiaGene study ( = 1571) and the Hoorn DCS cohort ( = 5409). Mono-sialylated apolipoprotein-CIII (apo-CIII ) was associated with a reduced risk of retinopathy (β = -7.215, 95% CI -11.137 to -3.294) whereas disialylated apolipoprotein-CIII (apo-CIII ) was associated with an increased risk (β = 5.309, 95% CI 2.279 to 8.339). A variant of the -gene (rs4846913), previously linked to lower apo-CIII , was associated with a decreased prevalence of retinopathy (OR = 0.739, 95% CI 0.575 to 0.951). Higher apo-CIII levels were associated with neuropathy (β = 7.706, 95% CI 2.317 to 13.095) and lower apo-CIII with macrovascular complications (β = -9.195, 95% CI -15.847 to -2.543). In conclusion, apo-CIII glycosylation was associated with the prevalence of micro- and macrovascular complications of diabetes. Moreover, a variant in the -gene was associated with apo-CIII glycosylation and retinopathy, suggesting a causal effect. The findings facilitate a molecular understanding of the pathophysiology of diabetes complications and warrant consideration of apo-CIII glycosylation as a potential target in the prevention of diabetes complications.