PLIN1 Variants in Precocious ACS (SCAPLIN)

Public Assistance-Hospitals of Marseille (AP-HM)

Status

Enrolling

Conditions

Acute Coronary Syndrome

Treatments

Genetic: PLIN1 gene sequencing

Study type

Interventional

Funder types

Other

Identifiers

NCT04904432

2021-06

Details and patient eligibility

About

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.

Enrollment

200 estimated patients

Sex

All

Ages

10 to 55 years old

Volunteers

No Healthy Volunteers

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.