GWAS and EWAS in Patients With Erdheim-Chester Disease

Recruiting

• Conditions: Erdheim-Chester Disease
• Interventions: Genetic: Presence of polymorphisms

• Registration Number: NCT06332183
• Lead Sponsor: Augusto Vaglio

Brief Summary

Erdheim-Chester Disease (ECD) is a rare form of histiocytosis characterized by the proliferation of blood cells, known as histiocytes, which infiltrate various organs and tissues, often causing irreversible damage. The causes of the condition are still unknown, and although some mutations in genes involved in cell proliferation have been identified, other factors may be involved. Susceptibility to developing rare diseases like ECD is typically associated with genetic factors, including DNA polymorphisms and epigenetic modifications.

This study aims to analyze the entire genome of a large cohort of patients with ECD and healthy controls to determine whether there are polymorphisms and epigenetic variants associated with susceptibility to developing the disease. The study could thus clarify the genetic predisposition to ECD development, provide insights into disease pathogenic mechanisms, and identify proteins or cellular mechanisms potentially targeted by specific treatments.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-07-17
• Study First Submitted: 2024-02-21
• Status Verified: 2024-03
• Study First Submitted QC: 2024-03-18
• Last Update Submitted: 2024-03-18
• Study First Posted: 2024-03-27
• Last Update Posted: 2024-03-27
• Primary Completion: 2024-07-01
• Study Completion: 2024-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• ECD with histological confirmation of disease

Exclusion criteria:

• previously treated patients (for methylation and gene expression)

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Presence of polymorphisms	Presence of polymorphisms	Statistical analysis of GWAS data, Genome-wide methylation pattern analysis, Integration of GWAS data and methylation data (meQTL analysis), Pathway enrichment analysis

Primary Outcome Measures

Name	Time	Method
Polymorphisms and genetic variants correlated with disease development	5 years	To investigate the presence of polymorphisms and genetic variants correlated with disease development, through a GWAS study. This task will be carried out by analyzing the frequency of the identified polymorphisms in patients and controls
Gene expression in Erdheim-Chester disease	5 years	To investigate the correlation between genetic variants or epigenetic profiles associated with the disease (previous outcomes) and specific clinical manifestations (organ involvement, somatic mutations, response to treatment, survival)
Methylation in Erdheim-Chester disease	5 years	To identify differences in gene methylation between patients with ECD and healthy controls, through an EWAS study. This task will be carried out by analyzing the grade of methylation in patients and controls

Trial Locations

Locations (5)

Genetics Lab, CSIC; 🇪🇸 Granada, Spain

AOU Parma; 🇮🇹 Parma, Italy

Hopital Pitié Salpetrière; 🇫🇷 Paris, France

IRCCS Ospedale San Raffaele; 🇮🇹 Milano, Italy

Meyer Children's Hospital IRCCS; 🇮🇹 Florence, Italy