DNA Methylation and Lung Disease in Cystic Fibrosis (METHYLCF)

Lung disease progression is variable among cystic fibrosis (CF) patients and depends on DNA mutations in the CFTR gene, polymorphic variations in disease-modifier genes and environmental exposure. The contribution of genetic factors has been extensively investigated, whereas the mechanism whereby environmental factors modulate the lung disease is unknown. Because these factors can affect the epigenome, investigators hypothesized that DNA methylation variations at disease-modifier genes modulate the lung function in CF patients.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Other: nasal epithelial; Other: Blood sampling

Detailed Description

Lung disease progression is variable among cystic fibrosis (CF) patients and depends on DNA mutations in the CFTR gene, polymorphic variations in disease-modifier genes and environmental exposure. The contribution of genetic factors has been extensively investigated, whereas the mechanism whereby environmental factors modulate the lung disease is unknown. Because these factors can affect the epigenome, investigators hypothesized that DNA methylation variations at disease-modifier genes modulate the lung function in CF patients.

The investigators analyzed DNA methylation levels in the promoter of fourteen lung disease-modifier genes and showed that DNA methylation levels are altered in nasal epithelial and blood cell samples from CF patients. This study disclosed slightly, but significantly differentially methylated regions that collectively may modulate lung disease severity. It also highlighted that complex relationships between genetic and epigenetic factors contribute to the phenotypic variability of CF patients.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • Uhmontpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• >18 years old
• homozygous for the F508del mutation

Exclusion Criteria:

• subjects who have an active CF exacerbation or a recent viral infection on the day of biological samples collection;
• pregnant women;
• patients who are included in interventional medical trials;
• patients who had lung transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• 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: CF patients; CF patients with the same procedures as in the usual management of routine care, only the sampling nasal epithelial cells will be added and blood sampling will be collected for this study	Other: nasal epithelial; CF patients with the same procedures as in the usual management of routine care, only the sampling nasal epithelial cells will be added; Other: Blood sampling; CF patients with the same procedures as in the usual management of routine care, only the sampling 5ml additional blood will be taken

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DNA methylation levels (chemical changes)	DNA methylation levels (chemical changes)	D0 (day of inclusion)

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; Vaincre la Mucoviscidose
• Investigators: Principal Investigator: Raphaël CHIRON, MD, University Hospital, Montpellier

Publications and helpful links

General Publications

• Magalhaes M, Tost J, Pineau F, Rivals I, Busato F, Alary N, Mely L, Leroy S, Murris M, Caimmi D, Claustres M, Chiron R, De Sario A. Dynamic changes of DNA methylation and lung disease in cystic fibrosis: lessons from a monogenic disease. Epigenomics. 2018 Aug;10(8):1131-1145. doi: 10.2217/epi-2018-0005. Epub 2018 Jul 27.
• Magalhaes M, Rivals I, Claustres M, Varilh J, Thomasset M, Bergougnoux A, Mely L, Leroy S, Corvol H, Guillot L, Murris M, Beyne E, Caimmi D, Vachier I, Chiron R, De Sario A. DNA methylation at modifier genes of lung disease severity is altered in cystic fibrosis. Clin Epigenetics. 2017 Feb 14;9:19. doi: 10.1186/s13148-016-0300-8. eCollection 2017.
• Pineau F, Caimmi D, Magalhaes M, Fremy E, Mohamed A, Mely L, Leroy S, Murris M, Claustres M, Chiron R, De Sario A. Blood co-expression modules identify potential modifier genes of diabetes and lung function in cystic fibrosis. PLoS One. 2020 Apr 17;15(4):e0231285. doi: 10.1371/journal.pone.0231285. eCollection 2020.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: August 16, 2016
• First Submitted That Met QC Criteria: August 30, 2016
• First Posted (Estimated): August 31, 2016

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: DNA methylation; Epigenetics; Lung disease; Modifier genes
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lung Diseases; Cystic Fibrosis; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: 9133

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED