Skip to main content
main-content

01.12.2018 | Research | Ausgabe 1/2018 Open Access

Respiratory Research 1/2018

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

Zeitschrift:
Respiratory Research > Ausgabe 1/2018
Autoren:
Anna Beckmeyer-Borowko, Medea Imboden, Faisal I. Rezwan, Matthias Wielscher, Andre F. S. Amaral, Ayoung Jeong, Emmanuel Schaffner, Juha Auvinen, Sylvain Sebert, Ville Karhunen, Robert Bettschart, Alexander Turk, Marco Pons, Daiana Stolz, Florian Kronenberg, Ryan Arathimos, Gemma C. Sharp, Caroline Relton, Alexander J. Henderson, Marjo-Riitta Jarvelin, Deborah Jarvis, John W. Holloway, Nicole M. Probst-Hensch
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12931-018-0850-8) contains supplementary material, which is available to authorized users.
Anna Beckmeyer-Borowko, Medea Imboden, Faisal I. Rezwan, Matthias Wielscher, Andre F.S. Amaral are equal first author.
Marjo-Riitta Jarvelin, Deborah Jarvis, John W. Holloway, Nicole M. Probst-Hensch are equal senior author.

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.
Zusatzmaterial
Additional file 1: Table ES1. Meta-Analysis of the association of methylation at CpGs in the SERPINA* Gene Cluster with FVC level and decline in adult ever smokers from SAPALDIA, ECRHS and NFBC (n = 1076) and with circulating AAT concentrations in SAPALDIA (n = 561). Table ES2. Meta-Analysis of the association of methylation at 119 CpGs in the SERPINA* cluster with FEV1 level and decline in adult ever smokers from SAPALDIA, ECRHS and NFBC (n = 1076) and with circulating AAT concentrations in SAPALDIA (n = 561). Table ES3. Meta-analysis of the association of methylation at 119 CpGs in the SERPINA* gene cluster with FVC level and decline in adult ever smokers from SAPALDIA, ECRHS and NFBC (n = 1076) and with circulating AAT concentrations in SAPALDIA (n = 561). Table ES4. Meta-analysis of the association of methylation at 119 CpGs in the SERPINA* gene cluster with FEV1/FVC level and decline in adult ever smokers from SAPALDIA, ECRHS and NFBC (n = 1076) and with circulating AAT concentrations in SAPALDIA (n = 561). Table ES5. Association of methylation at 119 CpGs in the SERPINA* gene cluster with FEV1 level and decline in ALSPAC children exposed to tobacco smoke (n = 259). Table ES6. Association of methylation at 119 CpGs in the SERPINA* gene cluster with FVC level and decline in in ALSPAC children exposed to tobacco smoke (n = 259). Table ES7. Association of methylation at 119 CpGs in the SERPINA* gene cluster with FEV1/FVC level and decline in ALSPAC children exposed to tobacco smoke (n = 259). Table ES8. Association of methylation at 119 CpGs in the SERPINA* gene cluster with FEV1 level and decline in adult smokers from SAPALDIA, basic adjustment and adjustment for PIS and PIZ genotypes. Table ES9. Association of methylation at 119 CpGs in the SERPINA* gene cluster with FEV1/FVC level and decline in adult smokers from SAPALDIA, basic adjustment and adjustment for PIS and PIZ genotypes. (DOCX 349 kb)
12931_2018_850_MOESM1_ESM.docx
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2018

Respiratory Research 1/2018 Zur Ausgabe

Neu im Fachgebiet Innere Medizin

Meistgelesene Bücher aus der Inneren Medizin

2017 | Buch

Rheumatologie aus der Praxis

Entzündliche Gelenkerkrankungen – mit Fallbeispielen

Dieses Fachbuch macht mit den wichtigsten chronisch entzündlichen Gelenk- und Wirbelsäulenerkrankungen vertraut. Anhand von über 40 instruktiven Fallbeispielen werden anschaulich diagnostisches Vorgehen, therapeutisches Ansprechen und der Verlauf …

Herausgeber:
Rudolf Puchner

2016 | Buch

Ambulant erworbene Pneumonie

Was, wann, warum – Dieses Buch bietet differenzierte Diagnostik und Therapie der ambulant erworbenen Pneumonie zur sofortigen sicheren Anwendung. Entsprechend der neuesten Studien und Leitlinien aller wichtigen Fachgesellschaften.

Herausgeber:
Santiago Ewig

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Innere Medizin und bleiben Sie gut informiert – ganz bequem per eMail.

© Springer Medizin 

Bildnachweise