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.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Comparison of post-prandial HDL particles
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Screening
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Affiliation to a national social security scheme
- •Age between 18 and 60 years old
- •Male subjects
- •Participants harboring either a B2 (genotype AA) allele or a B1 (genotype GG) in TaqIB polymorphism of CETP gene
- •Fasted plasmatic triglyceridemia < 300 mg/dL
- •Free prior and informed written consent given by the participant
排除标准
- •Participants with an history of symptomatic cardio-vascular disease (infarct, angina pectoris, acute coronary syndrome, cardiac surgery, endoluminal coronal intervention, stroke, symptomatic peripheral artery disease) within 6 months prior to inclusion.
- •Triglyceridemia > 3 g/L
- •Participants having other lipid-lowering agents than statin (fibrate, niacin, ezetimibe)
- •Participants having a treatment (either systemic or local) which might interfere with the evaluation of study parameters.
- •Excessive alcohol consumption, or any drug addiction. An excessive alcohol consumption is superior to 21 time 30 mL of alcohol or 120 mL of wine or 355 mL of beer.
- •Regular smoker or smoking cessation within the last year
- •Significant abnormality on the full blood count or plasmatic and urinary biochemistry analysis.
- •Chronic or acute disease either life threatening or able to modify study results, including among others :
- •Renal diseases : nephrotic syndrome, chronic kidney failure and/or creatininemia > 1.7 time the upper limit of normal (ULN).
- •Hypothyroidism defined by thyroid-stimulating hormone > 2x ULN
- •Hepatobiliary disease or viral hepatitis B or C confirmed by transaminases > 2x ULN or alkaline phosphatase > 1.5x ULN or total bilirubinemia > 1.5x ULN at screening.
- •Gastro-intestinal disorder or disease that might modify intestinal absorption, bariatric surgery.
- •Participant who might interfere with the quality of the study or might compromise the study according to the investigator.
- •Participant currently enrolled in another study or in the exclusion period of another study.
- •Participants with uncontrolled hypertension defined by a systolic blood pressure > 140 mmHg or a diastolic blood pressure > 90 mmHg.
- •Participants with a C reactive protein (CRP) > 5mg/L
- •Participants with a E2/E2 phenotype of apolipoprotein E.
- •Blood donation or product derived-from blood donation within the last 3 months prior to the test meal.
结局指标
主要结局
Comparison of post-prandial HDL particles
时间窗: before the meal (time = 0 hour) vs 2 hours after
Compare post-prandial HDL particles area under curve (AUC) between patients having B2 allele carriers (genotype AA) to B1 allele carriers (genotype GG)
次要结局
- Comparison of post-prandial HDL particles(before the meal (time = 0 hour), 2 hours, 4 hours, 6 hours and 8 hours after the meal)
- Efflux capacity of postprandial HDL particles(before the meal (time = 0 hour), 2 hours, 4 hours, 6 hours and 8 hours after the meal)
- Area under curves of triglyceridemia of apoB100 and apoB48(before the meal (time = 0 hour), 2 hours, 4 hours, 6 hours and 8 hours after the meal)
- Plasmatic concentrations of apoB100(before the meal (time = 0 hour), 2 hours, 4 hours, 6 hours and 8 hours after the meal)
- Correlation between the area under curve of triglyceridemia and the efflux capacity of HDL particles.(before the meal (time = 0 hour), 2 hours, 4 hours, 6 hours and 8 hours after the meal)
- Comparison of post-prandial HDL particles(before the meal (time = 0 hour), 2 hours, 4 hours, 6 hours and 8 hours after the meal)
- Efflux capacity of postprandial HDL particles(before the meal (time = 0 hour), 2 hours, 4 hours, 6 hours and 8 hours after the meal)
- Area under curves of triglyceridemia of apoB100 and apoB48(before the meal (time = 0 hour), 2 hours, 4 hours, 6 hours and 8 hours after the meal)
- Plasmatic concentrations of apoB100(before the meal (time = 0 hour), 2 hours, 4 hours, 6 hours and 8 hours after the meal)
- Correlation between the area under curve of triglyceridemia and the efflux capacity of HDL particles.(before the meal (time = 0 hour), 2 hours, 4 hours, 6 hours and 8 hours after the meal)