NCT03109067

Genetic and Metabolism of Post-prandial HDL Particles

Influence of TaqIB (rs708272) Polymorphism in Cholesteryl Ester Transfer Protein (CETP) Gene on Functionality of HDL Particles, in the Pathway of Reverse Transport of Fasting and Post-prandial Cholesterol.

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 100 (actual)
• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France · Other Government
• Sex: Male
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

Reverse cholesterol transport (RCT) pathway explains the anti-atherosclerosis role of HDL. Post prandial hypertriglyceridemia is highly predictive of atherosclerosis. TaqIB polymorphism in CETP gene plays a role on HDL particles, and might give a link between TaqIB polymorphism and the cardioprotective efficiency of HDL particles. Our main objective was to compare post-prandial HDL particles between patients having B2 allele carriers (genotype AA) to B1 allele carriers (genotype GG), and their ability to mediate cellular cholesterol efflux, via SR-BI Scavenger Receptor class B type I (SR-BI) , ABCG1 and ABCA1 pathways.

Detailed description

Background: This trial focuses on anti-atherogenic properties functions of HDL lipoproteins, particularly those linked to reverse transport cholesterol (RCT) pathway, genetic factors involved in plasmatic HDL-C and post-prandial metabolism. The post-prandial period is associated with an activation of the RCT with an increase in Cholesteryl ester transfer protein (CETP), in plasmatic HDL particles. There is also an increase of HDL particles ability to mediate cellular cholesterol efflux, via SR-BI and ABCG1 pathways. TaqIB polymorphism is associated with a variation of the plasma to mediate cellular cholesterol efflux. Aim of the study: The investigators were aiming to test the hypothesis that the genetic variability of HDL-C is associated with structural and functional variability of post-prandial HDL particles and particularly in their ability to mediate the initial step of RCT. Intervention: The study aimed to include n=50 patients with a TaqIB AA polymorphism and 50 patients with a GG TaqIB polymorphism. Blood samples were performed fasted, before and after intake of a standardized test meal at 5 different time : H0 before the meal, H2, H4, H6 and H8 after the meal. Explorations: For the fasted sample a full lipidic assessment was performed including the dosing of: triglyceridemia, HDL-C, apolipoprotein B (apoB), apolipoprotein AI. The plasmatic kinetic of triglyceridemia, apoB100, apo-48 and the activity of CETP was performed on each sample. HDL particles were also explored with qualitative and quantitative assessment of the HDL fractions ability to mediate cholesterol efflux via each pathway : SR-BI, ABCA1 and ABCG1 in our cellular models. The study therefore aimed to improve our knowledge of molecular mechanisms involved in HDL particles dysfunction in metabolic diseases.

Conditions

• Healthy Volunteers

Interventions

Type	Name	Description
OTHER	Standardized meal	Blood samples performed at 5 different times : H0 before the meal, H2, H4, H6 and H8 after the meal

Timeline

• Start date: 2011-09-21
• Primary completion: 2015-11-21
• Completion: 2015-11-21
• First posted: 2017-04-12
• Last updated: 2025-09-03

Locations

1 site across 1 country: France