Abstract(s) :

(Anglais) Background: Proprotein convertase subtilisin/kexin 9 (PCSK9) is an important regulator of low-density lipoprotein cholesterol (LDL-c) via LDL-receptor (LDLR) down regulation. PCSK9 inhibitors (PCSK9i) emerged as the most effective LDL-c-lowering drugs. But whether the long-term use of PCSK9i is associated with diabetes mellitus (DM) in humans is not clear. The enhanced expression of LDLR promoted by PCSK9 knock-out in mice triggers the apoptotic death of pancreatic β-cells subsequent to cholesterol overcharge. This in turn reduces insulin secretion and impairs glucose metabolism. The aim of this study was to identify the PCSK9 genetic variants and explore their association with the onset of type 2 DM (T2DM) or its complications. Methods: Socio-demographic and anthropometric data and blood samples were collected from T2DM subjects. Serum glucose was measured by Glucose Oxidase and Peroxidase method (ELITech Group, Puteaux, France), insulin by sandwich ELISA (ALPCO, Salem, New Hampshire, USA) and PCSK9 gene sequencing was performed by Sanger method. Results: Study population was aged of 61±9 years. Two genomic variants reported in African population were identified, namely c.1026A>G (p.Gln342) and the intronic variant c.1180+174 A>G. The p.Gln342 was present in 80% of study participants (62.50% female; 37.50% male), whereas the intronic variant c.1180+174 A>G was in 40% of subjects (75% female; 25% male). The fasting insulin and glycemia were 6.09 (± 5.19) µIU/mL and 219 (±92) mg/dL respectively. A positive correlation was observed between insulin and glycemia (r=0.61). Conclusion: Preliminary results suggest that subjects carrying both variants of PSCK9 displayed insulin impairment and higher systolic blood pressure.

• (Anglais) adiponectin
• (Anglais) PCSK9
• (Anglais) genetic variants
• (Anglais) cardiovascular diseases
• (Anglais) insulin
• (Anglais) type 2 diabetes