Genetic and Metabolism of Post-prandial HDL Particles
Condition: Healthy Volunteers
Study type: Interventional

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.
    

Intervention name(s): Standardized meal
Intervention type(s): Other
Intervention description(s): Blood samples performed at 5 different times : H0 before the meal, H2, H4, H6 and H8 after the meal
Intervention model: Single Group Assignment
Intervention model description: Same intervention for everyone, two different groups
Masking: None (Open Label)
Primary purpose: Screening
Keywords: Cholesterol, HDL, Postprandial Period, Polymorphism, Genetic