AHRR hypomethylation, lung function, lung function decline and respiratory symptoms

Jakob B Kodal; Camilla J Kobylecki; Signe Vedel-Krogh; Børge G Nordestgaard; Stig E Bojesen

doi:10.1183/13993003.01512-2017

AHRR hypomethylation, lung function, lung function decline and respiratory symptoms

Jakob B Kodal, Camilla J Kobylecki, Signe Vedel-Krogh, Børge G Nordestgaard, Stig E Bojesen

16 Citations (Scopus)

Abstract

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.AHRR methylation 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 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 (95% CI 1.18-1.45) for chronic bronchitis and 1.21 (95% CI 1.13-1.30) for any respiratory symptoms.AHRR hypomethylation was associated with low lung function, steeper lung function decline, and respiratory symptoms.

Original language	English
Article number	1701512
Journal	The European Respiratory Journal
Volume	51
Issue number	3
ISSN	0903-1936
DOIs	https://doi.org/10.1183/13993003.01512-2017
Publication status	Published - 1 Mar 2018

Access to Document

10.1183/13993003.01512-2017

1701512.full.pdfFinal published version, 686 KB

Cite this

@article{c95c91b68a9c44ed8b4b7fb95e2c5344,

title = "AHRR hypomethylation, lung function, lung function decline and respiratory symptoms",

abstract = "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.AHRR methylation 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 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 (95% CI 1.18-1.45) for chronic bronchitis and 1.21 (95% CI 1.13-1.30) for any respiratory symptoms.AHRR hypomethylation was associated with low lung function, steeper lung function decline, and respiratory symptoms.",

author = "Kodal, {Jakob B} and Kobylecki, {Camilla J} and Signe Vedel-Krogh and Nordestgaard, {B{\o}rge G} and Bojesen, {Stig E}",

note = "Copyright {\textcopyright}ERS 2018.",

year = "2018",

month = mar,

day = "1",

doi = "10.1183/13993003.01512-2017",

language = "English",

volume = "51",

journal = "Acta tuberculosea Scandinavica",

issn = "0904-1850",

publisher = "European Respiratory Society",

number = "3",

}

TY - JOUR

T1 - AHRR hypomethylation, lung function, lung function decline and respiratory symptoms

AU - Kodal, Jakob B

AU - Kobylecki, Camilla J

AU - Vedel-Krogh, Signe

AU - Nordestgaard, Børge G

AU - Bojesen, Stig E

PY - 2018/3/1

Y1 - 2018/3/1

N2 - 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.AHRR methylation 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 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 (95% CI 1.18-1.45) for chronic bronchitis and 1.21 (95% CI 1.13-1.30) for any respiratory symptoms.AHRR hypomethylation was associated with low lung function, steeper lung function decline, and respiratory symptoms.

AB - 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.AHRR methylation 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 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 (95% CI 1.18-1.45) for chronic bronchitis and 1.21 (95% CI 1.13-1.30) for any respiratory symptoms.AHRR hypomethylation was associated with low lung function, steeper lung function decline, and respiratory symptoms.

U2 - 10.1183/13993003.01512-2017

DO - 10.1183/13993003.01512-2017

M3 - Journal article

C2 - 29348151

SN - 0904-1850

VL - 51

JO - Acta tuberculosea Scandinavica

JF - Acta tuberculosea Scandinavica

IS - 3

M1 - 1701512

ER -

AHRR hypomethylation, lung function, lung function decline and respiratory symptoms

Abstract

Access to Document

Fingerprint

Cite this