Milena Magalhães1,2, Jörg Tost3, Fanny Pineau1, Isabelle Rivals4, Florence Busato3, Nathan Alary1, Laurent Mely5, Sylvie Leroy6, Marlène Murris7, Davide Caimmi8, Mireille Claustres1,9, Raphaël Chiron8, Albertina De Sario1. 1. Laboratoire de Génétique de Maladies Rares - EA7402 Montpellier University - Montpellier - France. 2. Laboratory of Biological System Modeling - INCT/IDN, CDTS - Rio de Janeiro - Brazil. 3. Laboratory for Epigenetics & Environment - Centre National de Recherche en Génomique Humaine - CEA - Institut de Biologie François Jacob - Evry - France. 4. Equipe de Statistique Appliquée - ESPCI Paris - PSL Research University - UMRS1158 - Paris - France. 5. CRCM, Renée Sabran Hospital - CHU Lyon - Hyères - France. 6. CRCM, Pasteur Hospital - CHU Nice - Nice - France. 7. CRCM, Larrey Hospital - CHU Toulouse - Toulouse - France. 8. CRCM, Arnaud de Villeneuve Hospital - CHU Montpellier - Montpellier - France. 9. Laboratoire de Génétique Moléculaire - CHU Montpellier - Montpellier - France.
Abstract
AIM: To assess whether DNA methylation levels account for the noninherited phenotypic variations observed among cystic fibrosis (CF) patients. PATIENTS & METHODS: Using the 450 K BeadChip, we profiled DNA methylation in nasal epithelial cells collected from 32 CF patients and 16 controls. RESULTS: We detected substantial DNA methylation differences up to 55% (median β change 0.13; IQR: 0.15-0.11) between CF patients and controls. DNA methylation levels differed between mild and severe CF patients and correlated with lung function at 50 CpG sites. CONCLUSION: In CF samples, dynamic changes of DNA methylation occurred in genes responsible for the integrity of the epithelium and the inflammatory and immune responses, were prominent in transcriptionally active genomic regions and were over-represented in enhancers active in lung tissues. ( Clinicaltrials.gov NCT02884622).
AIM: To assess whether DNA methylation levels account for the noninherited phenotypic variations observed among cystic fibrosis (CF) patients. PATIENTS & METHODS: Using the 450 K BeadChip, we profiled DNA methylation in nasal epithelial cells collected from 32 CFpatients and 16 controls. RESULTS: We detected substantial DNA methylation differences up to 55% (median β change 0.13; IQR: 0.15-0.11) between CFpatients and controls. DNA methylation levels differed between mild and severe CFpatients and correlated with lung function at 50 CpG sites. CONCLUSION: In CF samples, dynamic changes of DNA methylation occurred in genes responsible for the integrity of the epithelium and the inflammatory and immune responses, were prominent in transcriptionally active genomic regions and were over-represented in enhancers active in lung tissues. ( Clinicaltrials.gov NCT02884622).
Entities:
Keywords:
DNA methylation; cystic fibrosis; epigenetics and disease
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