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

Anna Beckmeyer-Borowko*, Medea Imboden, Faisal Rezwan, Matthias Wielscher, Andre F. S. Amaral, Ayoung Jeong, Emmanuel Schaffner, Juha Auvinen, Sylvian Sebert, Villa Karhunen, Robert Bettschart, Alexander Turk, Marco Pons, Daiana Stolz, Florian Kronenberg, Ryan Arathimos, Gemma C. Sharp, Caroline Relton, Alexander J. Henderson, Marjo-Rittaa JarvelinDeborah Jarvis, John W. Holloway, Nicole Probst-Hensch

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

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.
Original languageEnglish
Article number156
JournalRespiratory Research
Volume19
Issue number1
DOIs
Publication statusPublished - 22 Aug 2018

Keywords

  • Alpha-1 antitrypsin
  • Chronic obstructive pulmonary disease; SERPINA1 methylation
  • DNA methylation
  • Epigenetics
  • Population based study
  • Smoking
  • Humans
  • Middle Aged
  • Child, Preschool
  • Infant
  • Male
  • alpha 1-Antitrypsin/genetics
  • Tobacco Smoke Pollution/adverse effects
  • Young Adult
  • Europe/epidemiology
  • Adult
  • DNA Methylation/physiology
  • Female
  • Lung/drug effects
  • Child
  • Infant, Newborn
  • Cross-Sectional Studies
  • Population Surveillance/methods
  • Tobacco/adverse effects
  • Adolescent
  • Aged
  • Longitudinal Studies
  • Cohort Studies
  • Nicotiana/adverse effects

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