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SERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts

SERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts
SERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts
Background

The pathophysiological role of SERPINA1 in respiratory health may be more strongly determined by the regulation of its expression than by common genetic variants. A family based study of predominantly smoking adults found methylation at two Cytosine-phosphate-Guanine sites (CpGs) in SERPINA1 gene to be associated with chronic obstructive pulmonary disease risk. The objective of this study was to confirm the association of lung function with SERPINA1 methylation in general population samples by testing a comprehensive set of CpGs in the SERPINA gene cluster. We considered lung function level and decline in adult smokers from three European population-based cohorts and lung function level and growth in tobacco-smoke exposed children from a birth cohort.

Methods

DNA methylation using Illumina Infinium Human Methylation 450 k and EPIC beadchips and lung function were measured at two time points in 1076 SAPALDIA, ECRHS and NFBC adult cohort participants and 259 ALSPAC children. Associations of methylation at 119 CpG sites in the SERPINA gene cluster (PP4R4-SERPINA13P) with lung functions and circulating alpha-1-antitripsin (AAT) were assessed using multivariable cross-sectional and longitudinal regression models.

Results

Methylation at cg08257009 in the SERPINA gene cluster, located 32 kb downstream of SERPINA1, not annotated to a gene, was associated with FEV1/FVC at the Bonferroni corrected level in adults, but not in children. None of the methylation signals in the SERPINA1 gene showed associations with lung function after correcting for multiple testing.

Conclusions

The results do not support a role of SERPINA1 gene methylation as determinant of lung function across the life course in the tobacco smoke exposed general population exposed.
1465-9921
1-14
Beckmeyer-Borowko, Anna
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Imboden, Medea
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Rezwan, Faisal I.
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Wielscher, Matthias
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Amaral, Andre F.S.
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Jeong, Ayoung
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Schaffner, Emmanuel
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Auvinen, Juha
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Sebert, Sylvain
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Karhunen, Ville
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Bettschart, Robert
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Turk, Alexander
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Pons, Marco
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Stolz, Daiana
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Kronenberg, Florian
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Arathimos, Ryan
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Sharp, Gemma C.
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Relton, Caroline
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Henderson, Alexander J.
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Jarvelin, Marjo-Riitta
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Jarvis, Deborah
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Holloway, John W.
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Probst-Hensch, Nicole M.
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Beckmeyer-Borowko, Anna
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Imboden, Medea
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Rezwan, Faisal I.
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Wielscher, Matthias
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Amaral, Andre F.S.
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Jeong, Ayoung
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Schaffner, Emmanuel
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Auvinen, Juha
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Sebert, Sylvain
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Karhunen, Ville
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Bettschart, Robert
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Turk, Alexander
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Pons, Marco
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Stolz, Daiana
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Kronenberg, Florian
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Arathimos, Ryan
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Sharp, Gemma C.
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Relton, Caroline
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Henderson, Alexander J.
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Jarvelin, Marjo-Riitta
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Jarvis, Deborah
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Holloway, John W.
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Probst-Hensch, Nicole M.
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Beckmeyer-Borowko, Anna, Imboden, Medea, Rezwan, Faisal I., Wielscher, Matthias, Amaral, Andre F.S., Jeong, Ayoung, Schaffner, Emmanuel, Auvinen, Juha, Sebert, Sylvain, Karhunen, Ville, Bettschart, Robert, Turk, Alexander, Pons, Marco, Stolz, Daiana, Kronenberg, Florian, Arathimos, Ryan, Sharp, Gemma C., Relton, Caroline, Henderson, Alexander J., Jarvelin, Marjo-Riitta, Jarvis, Deborah, Holloway, John W. and Probst-Hensch, Nicole M. (2018) SERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts. Respiratory Research, 19 (1), 1-14. (doi:10.1186/s12931-018-0850-8).

Record type: Article

Abstract

Background

The pathophysiological role of SERPINA1 in respiratory health may be more strongly determined by the regulation of its expression than by common genetic variants. A family based study of predominantly smoking adults found methylation at two Cytosine-phosphate-Guanine sites (CpGs) in SERPINA1 gene to be associated with chronic obstructive pulmonary disease risk. The objective of this study was to confirm the association of lung function with SERPINA1 methylation in general population samples by testing a comprehensive set of CpGs in the SERPINA gene cluster. We considered lung function level and decline in adult smokers from three European population-based cohorts and lung function level and growth in tobacco-smoke exposed children from a birth cohort.

Methods

DNA methylation using Illumina Infinium Human Methylation 450 k and EPIC beadchips and lung function were measured at two time points in 1076 SAPALDIA, ECRHS and NFBC adult cohort participants and 259 ALSPAC children. Associations of methylation at 119 CpG sites in the SERPINA gene cluster (PP4R4-SERPINA13P) with lung functions and circulating alpha-1-antitripsin (AAT) were assessed using multivariable cross-sectional and longitudinal regression models.

Results

Methylation at cg08257009 in the SERPINA gene cluster, located 32 kb downstream of SERPINA1, not annotated to a gene, was associated with FEV1/FVC at the Bonferroni corrected level in adults, but not in children. None of the methylation signals in the SERPINA1 gene showed associations with lung function after correcting for multiple testing.

Conclusions

The results do not support a role of SERPINA1 gene methylation as determinant of lung function across the life course in the tobacco smoke exposed general population exposed.

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More information

Accepted/In Press date: 24 July 2018
e-pub ahead of print date: 22 August 2018
Published date: 22 August 2018

Identifiers

Local EPrints ID: 424568
URI: https://eprints.soton.ac.uk/id/eprint/424568
ISSN: 1465-9921
PURE UUID: a828fb17-10ff-4461-bcf2-cb31fe0a2a90
ORCID for Faisal I. Rezwan: ORCID iD orcid.org/0000-0001-9921-222X
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 05 Oct 2018 11:38
Last modified: 14 Mar 2019 01:50

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Contributors

Author: Anna Beckmeyer-Borowko
Author: Medea Imboden
Author: Matthias Wielscher
Author: Andre F.S. Amaral
Author: Ayoung Jeong
Author: Emmanuel Schaffner
Author: Juha Auvinen
Author: Sylvain Sebert
Author: Ville Karhunen
Author: Robert Bettschart
Author: Alexander Turk
Author: Marco Pons
Author: Daiana Stolz
Author: Florian Kronenberg
Author: Ryan Arathimos
Author: Gemma C. Sharp
Author: Caroline Relton
Author: Alexander J. Henderson
Author: Marjo-Riitta Jarvelin
Author: Deborah Jarvis
Author: Nicole M. Probst-Hensch

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