Source: International Congress 2016 – Important factors, besides smoking, that relate to lung function and decline in lung function
Disease area: Airway diseases, Paediatric lung diseases

Abstract

Background:Preterm birth is strongly associated with increased risk of respiratory morbidity from birth until adulthood. Perinatal factors have been associated with epigenetic changes in children, and our aim was to investigate the association between gestational age (GA) and DNA methylation patterns in newborns. In addition, expression patterns of identified genes during lung development were explored.Methods:We performed an epigenome-wide analysis of DNA methylation using the Illumina 450K platform. DNA methylation was measured in cord blood of 340 newborn babies (GA 31-42 weeks) from the Mechanisms of the Development of Allergy (MeDALL) study (French EDEN and Spanish INMA cohorts). RNA expression patterns in the developing human lung during the pseudoglandular (GA 7-16 weeks) and canalicular (17-26 weeks) stages of development (GEO accession number GSE14334) were investigated.Results:In total, 202 CpG sites corresponding to 130 genes associated with GA at the genome-wide significant level (p < 1.1 x 10 ^-07). Sixty of the 130 identified genes were differentially expressed during human lung development (FDR p < 0.05). The greatest magnitude of effect was observed for HLA-E, YPEL3 and MAN1C1 with increased expression pattern and FKBP5 and CDK6 with decreased expression pattern across developmental stages.Conclusions: We identified 130 differentially methylated genes associated with gestational age at birth; 60 of which were differentially expressed during human lung development. We believe that our epigenetic and fetal lung transcriptomic analyses may provide important insights about mechanisms related to negative long-term respiratory health outcomes of preterm birth.


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Simon Kebede Merid (Stockholm, Sweden), Simon Kebede Merid, Cheng-Jian Xu, Mariona Bustamante, Nour Baiz, Isabella Annesi-Maesano, Josep M. Antó, Jean Bousquet, Olena Gruzieva, Juha Kere, Ashish Kumar, Göran Pershagen, Dirkje Postma, Jordi Sunyer, Cilla Söderhäll, Kelan Tantisira, Scott T. Weiss, Gerard H. Koppelman, Erik Melén. Differentially methylated genes related to gestational age are also expressed during fetal lung development. Eur Respir J 2016; 48: Suppl. 60, 5004

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