TY - JOUR T1 - <em>AHRR</em> hypomethylation, lung function, lung function decline, and respiratory symptoms JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01512-2017 SP - 1701512 AU - Jakob B. Kodal AU - Camilla J. Kobylecki AU - Signe Vedel-Krogh AU - Børge G. Nordestgaard AU - Stig E. Bojesen Y1 - 2018/01/01 UR - http://erj.ersjournals.com/content/early/2018/01/05/13993003.01512-2017.abstract N2 - Introduction: Epigenome wide association studies have shown a consistent association between smoking exposure and hypomethylation in the aryl hydrocarbon receptor repressor(AHRR) gene(cg05575921). We tested the hypothesis that AHRR hypomethylation is associated with low lung function, steeper lung function decline, and respiratory symptoms in the general population.Methods: AHRR methylation extent was measured in 9113 individuals from the 1991-1994 examination of the Copenhagen City Heart Study, using bisulfite treated leucocyte DNA. Spirometry at the time of blood sampling was available for all individuals. Furthermore, for 4532 of these individuals lung function was measured again in 2001–2003.Results: Cross-sectionally, a 10% lower methylation extent was associated with a 0.2 z-score(95% confidence interval:0.1–0.2) lower forced expiratory volume in 1 s(FEV1) after multivariable adjustment including smoking. Hypomethylation was also associated with a lower z-score for both forced vital capacity(FVC) and FEV1/FVC. In prospective analyses, individuals in the lowest versus highest tertile of methylation extent had a steeper decline in FEV1/height3(p for examination×methylation interaction=0.003), and FVC/height3(p=0.01), but not FEV1/FVC(p=0.08). Multivariable adjusted odds ratios per 10% lower methylation extent were 1.31(1.18–1.45) for chronic bronchitis and 1.21(1.13–1.30) for any respiratory symptoms.Conclusion: AHRR hypomethylation was associated with low lung function, steeper lung function decline, and respiratory symptoms.AHRR hypomethylation is associated with low lung function, steeper lung function decline, and respiratory symptoms.FootnotesThis 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. ER -