
pmid: 29348151
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 thatAHRRhypomethylation is associated with low lung function, steeper lung function decline, and respiratory symptoms in the general population.AHRRmethylation extent was measured in 9113 individuals from the 1991–1994 examination of the Copenhagen City Heart Study, using bisulfite-treated leukocyte DNA. Spirometry at the time of blood sampling was available for all individuals. Lung function was measured again for 4532 of these individuals in 2001–2003.Cross-sectionally, a 10% lower methylation extent was associated with a 0.2 z-score (95% CI 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 lowestversushighest 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 (95% CI 1.18–1.45) for chronic bronchitis and 1.21 (95% CI 1.13–1.30) for any respiratory symptoms.AHRRhypomethylation was associated with low lung function, steeper lung function decline, and respiratory symptoms.
Basic Helix-Loop-Helix Proteins, Male, Denmark, Epigenesis, Genetic, Humans, Prospective Studies, Registries, Lung, Aged, Genome, Human, Respiration, Smoking, DNA Methylation, Middle Aged, Respiratory Function Tests, Repressor Proteins, Cross-Sectional Studies, Multivariate Analysis, Female, Follow-Up Studies
Basic Helix-Loop-Helix Proteins, Male, Denmark, Epigenesis, Genetic, Humans, Prospective Studies, Registries, Lung, Aged, Genome, Human, Respiration, Smoking, DNA Methylation, Middle Aged, Respiratory Function Tests, Repressor Proteins, Cross-Sectional Studies, Multivariate Analysis, Female, Follow-Up Studies
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