PLIN1 Variants in Precocious ACS (SCAPLIN)

Not Applicable

Recruiting

• Conditions: Acute Coronary Syndrome
• Interventions: Genetic: PLIN1 gene sequencing

• Registration Number: NCT04904432
• Lead Sponsor: Assistance Publique Hopitaux De Marseille

Brief Summary

This study aims to identify a genetic predisposition factor of precocious acute coronary syndrome occurrence (ACS). ACS is a major public health problem and the first cause of mortality in the world. It can be due to several risk factor such as heredity. the investigators make the hypothesis that occurrence of early ACS (defined as \<50yo for men and \<55yo for women) could be the initiatory event of a mild form of genetic lipodystrophy . Our previous study shown an occurrence risk of ACS about 8.3 in patients carrying a mutation in the PLIN1 gene versus patients without a mutation. The PLIN1 gene encode for perilipin 1 protein localized on the lipid droplet surface. This protein phosphorylation activates the triglycerides lipolysis. Our goals in this study are multiple: to validate the high frequency of mutations in this gene in patients with early ACS, to determine differences in triglycerides metabolism and also relapse rate between carrier and non-carrier patients of mutation in PLIN1. Our first aim will be to carry out the inclusion of 200 patients with precocious ACS. This will allow us to obtain around 15 patients carrying a mutation in the PLIN1 gene based on our previous study. the investigators will reprogramme patients' cells (carrying or not a PLIN1 mutation) in human Induce Pluripotent Stem cells (hIPSc). These hIPSc will be differentiated in cell types of interest as adipocytes or macrophages. the investigators will then study triglycerides metabolism (lipid droplet formation, localization and phosphorylation of perlipin 1) in these cells and atheroma plaque formation. Finally, the investigators will study clinical data such as relapse rate and searching for correlation with PLIN1 mutation.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-04-15
• Study First Submitted QC: 2021-05-26
• Study First Posted: 2021-05-27
• Study Start: 2021-09-15
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-26
• Last Update Posted: 2022-10-27
• Primary Completion: 2023-06-01
• Study Completion: 2024-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Age of the patient when ACS occurs (between 18 and 50yo for men, between 18 and 55yo for women)
• Written informed consent

Exclusion Criteria

• Men <18yo or >50yo
• Women <18yo or >55yo
• ACS causes (toxic, coronary dissection)
• Congenital cardiac malformations
• Familial hypercholesterolaemia
• Pregnancy, breast-feeding women or vulnerable profile.
• Patient refusal to participate or previously included in a clinical research trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
young ACS patients	PLIN1 gene sequencing	-

Primary Outcome Measures

Name	Time	Method
PLIN1 mutation	1 month	sequencing PLIN1 gene to look for mutation
Lipid droplets	3 years	Analyze size of lipid droplets in differentiated hIPS cells

Secondary Outcome Measures

Name	Time	Method
relapse rate	1 year	Ischaemic relapse rate during the year of classical following-up

Trial Locations

Locations (1)

Assistance Publique Hôpitaux de Marseille; 🇫🇷 Marseille, France