Berita Kesehatan
Co-methylation analysis in lung tissue identifies pathways for fetal origins of COPD
Selasa, 02 Jun 2020 11:14:57

Priyadarshini Kachroo, Jarrett D. Morrow, Alvin T. Kho, Carrie A. Vyhlidal, Edwin K. Silverman, Scott T. Weiss, Kelan G. Tantisira, Dawn L. DeMeo

European Respiratory Journal 2020; DOI: 10.1183/13993003.02347-2019

Abstract

Chronic Obstructive Pulmonary Disease (COPD) likely has developmental origins, however the underlying molecular mechanisms are not fully identified. Investigation of lung tissue-specific epigenetic modifications such as DNA methylation using network approaches might facilitate insights linking in-utero smoke (IUS) exposure and risk for COPD in adulthood.

We performed genome-wide methylation profiling for adult lung DNA from 160 surgical samples and 78 fetal lung DNA samples isolated from discarded tissue from 8 to 18 weeks of gestation. Co-methylation networks were constructed to identify preserved modules that shared methylation patterns in fetal and adult lung tissues and associations with fetal IUS exposure, gestational age and COPD.

Weighted correlation networks highlighted preserved and co-methylated modules for both fetal and adult lung data associated with fetal IUS-exposure, COPD and lower adult lung function. These modules were significantly enriched for genes involved in embryonic organ development and specific inflammation-related pathways including Hippo, PI3K/AKT, Wnt, MAP-Kinase and TGF-beta signalling. Gestational age-associated modules were remarkably preserved for COPD and lung function and were also annotated to genes enriched for the Wnt and PI3K/AKT pathways.

Epigenetic network perturbations in fetal lung tissue exposed to IUS and of early lung development recapitulated in adult lung tissue from former smokers with COPD. Overlapping fetal and adult lung tissue network modules highlighted putative disease pathways supportive of exposure-related and age-associated developmental origins of COPD.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Kachroo has nothing to disclose.

Conflict of interest: Dr. Morrow reports grants from National Institutes of Health, during the conduct of the study.

Conflict of interest: Dr. Kho has nothing to disclose.

Conflict of interest: Dr. Vyhlidal reports grants from NIH, during the conduct of the study.

Conflict of interest: Dr. Silverman reports grants from NIH, during the conduct of the study; grants and other support from GlaxoSmithKline and grants from Bayer, outside the submitted work.

Conflict of interest: Dr. Weiss reports personal fees from UpToDate, outside the submitted work.

Conflict of interest: Dr. Tantisira reports grants from National Institutes of Health, during the conduct of the study.

Conflict of interest: Dr. DeMeo reports grants from National Institutes of Health, during the conduct of the study and grants from Bayer, outside the submitted work.

  • Received December 13, 2019.
  • Accepted May 21, 2020.
  • Copyright ©ERS 2020