PLIN1 Variants in Precocious ACS (SCAPLIN)

Involvement of Perilipin-1 Variants in Precocious Acute Coronary Syndrome

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Genetic: PLIN1 gene sequencing

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nathalie BONELLO-PALOT; Phone Number: +33 04 91 38 77 87; Email: nathalie.bonello@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13005
    • Recruiting
    • Assistance Publique Hopitaux de Marseille
    • Contact: Nathalie BONELLO-PALOT, Pharm.D, PhD
    • Principal Investigator: Laurent BONELLO, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: young ACS patients	Genetic: PLIN1 gene sequencing; One supplementary blood sample will be taken (compare to classical ACS treatment and follow up) to realize genetic analyse of PLIN1 gene, looking for mutations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PLIN1 mutation	sequencing PLIN1 gene to look for mutation	1 month
Lipid droplets	Analyze size of lipid droplets in differentiated hIPS cells	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
relapse rate	Ischaemic relapse rate during the year of classical following-up	1 year

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: April 15, 2021
• First Submitted That Met QC Criteria: May 26, 2021
• First Posted (Actual): May 27, 2021

Study Record Updates

• Last Update Posted (Actual): October 27, 2022
• Last Update Submitted That Met QC Criteria: October 26, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome
• Other Study ID Numbers: 2021-06

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No