Clinical Trial: HYPOCHOL : A Genetically-based Strategy to Identify New Targets in Cholesterol Metabolism

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: HYPOCHOL : A Genetically-based Strategy to Identify New Targets in Cholesterol Metabolism

Brief Summary: The aim of this study is to identify new targets in cholesterol metabolism thanks to a genetically-based strategy.

Detailed Summary:

The goal is to recruit 400 subjects: 200 adult subjects with familial hypobetalipoproteinemia (FHBL) (index cases) plus 200 additional related subjects in at least 10 large informative FHBL families, in which there is no known mutation in FHBL genes.

The patient care is modified: patient will have an Hospital Anxiety and Depression (HAD) questionnaire (focus on depressive syndrome), a food diary, and some additional blood analysis (including genetic analysis).

One of the main issue to recruit FHBL patients is the fact that they are asymptomatic and that FHBL is not identified as a serious illness by their general physicians.

Step-1. Excluding mutations in selected candidate genes As a first approach to screen candidate genes and exclude patients with known mutations, the investigators developed a custom design based on the Haloplex™ technology (Agilent® Technologies) to perform high-throughput sequencing of the coding regions of 10 genes, including those previously described in FHBL (apolipoprotein B (APOB), Proprotein convertase subtilisin/kexin type 9 (PCSK9)), Microsomal triglyceride transfer protein (MTP or ABL), chylomicron retention disease (CMRD), Secretion associated, Ras related GTPase (SARA2 gene), as well as 6 additional candidate genes in cholesterol metabolism (low density lipoprotein receptor (LDLR), Sortilin (SORT1), Inducible Degrader of the LDL receptor (IDOL), Cholesteryl ester transfer protein (CETP), Apolipoprotein E (ApoE) and Angiopoietin-like Protein 3 (ANGTPL3)). All the recruited index cases (n=200) will be genotyped to select only those without mutations in previously described genes, being approximately 50% of our index case cohort.

Step-2. Identification of informative families and exom
Sponsor: Nantes University Hospital

Current Primary Outcome: type and number of genetic abnormalities leading to FHBL [ Time Frame: ten years ]

To identify new gene involved in FHBL and determine genetic cause of FHBL (Patients with FHBL and their relatives will be recruited to establish familial forms of FHBL in large informative families with no mutations in known classical FHBL genes. This will allow perform genetic analysis using new approaches to genetic broadband (exome sequencing analysis + linkage analysis). This approach will allow specify which chromosomal regions are shared only by affected individuals, and identify new candidate genes).


Original Primary Outcome: type and number of genetic adnormalities leading to FHBL [ Time Frame: ten years ]

To identify new gene involved in FHBL and determine genetic cause of FHBL (Patients with FHBL and their relatives will be recruited to establish familial forms of FHBL in large informative families with no mutations in known classical FHBL genes. This will allow perform genetic analysis using new approaches to genetic broadband (exome sequencing analysis + linkage analysis). This approach will allow specify which chromosomal regions are shared only by affected individuals, and identify new candidate genes).


Current Secondary Outcome:

Original Secondary Outcome:

Information By: Nantes University Hospital

Dates:
Date Received: January 14, 2015
Date Started: February 2016
Date Completion: December 2028
Last Updated: February 5, 2016
Last Verified: February 2016