Human Fetal Lungs Harbor a Microbiome Signature
Denise Al Alam, Soula Danopoulos, Brendan H. Grubbs, Nur A’tikah Binte Mohamed Ali, Micheal MacAogain, Sanjay H. Chotirmall, David Warburton, Amit Gaggar, Namasivayam Ambalavanan, Charitharth Vivek Lal
Abstract
COPD (11,12). RARB is expressed in human lung tissue, bronchial epithelial cells, and airway smooth muscle cells (10), and knockout of this gene could lead to premature alveolar septation in mice (13), suggesting its fundamental function in lung development, normal physiology, and capacity.In this study, we observed the positive association between PAH exposure and hypermethylation in RARB promoter; a putative effect may exist on decreasing expression of RARB caused by PAHs.There was also a suggestive association of rs1529672-A allele with reduced RARB expression.Considering the important biological roles of RARB in lung development, we speculated that the decreased expression of RARB may act as the common target for PAH exposure and rs1529672, suggesting a possible mechanism underlying the statistical gene-environment interaction.Strengths of this study were the prospective design and results validation by two independent cohorts of populations with a wide range of PAH exposure.The limitations of this study included not investigating the SNPs reported after March 2017, along with variants in genes involved in PAH metabolism and related biological pathways.Future longitudinal studies in other ethnic populations and the well-designed functional studies are warranted to validate these associations and elucidate putative mechanisms for the PAH-RARB interaction in lung function impairment.In conclusion, the GWAS reported RARB rs1529672 may modify the effect of PAH exposure on annual FEV 1 /FVC decline.The results emphasize the urgency of reducing environmental PAH levels and the importance of lung function monitoring in the routine physical examination, especially for high-risk populations.