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

Respir Res 2018 Aug 22;19(1):156. Epub 2018 Aug 22.

Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002, Basel, Switzerland.

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 FEV/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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Source
http://dx.doi.org/10.1186/s12931-018-0850-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103990PMC
August 2018
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References

(Supplied by CrossRef)
Article in Lancet
SS Salvi et al.
Lancet 2009
Article in Mutat Res
YM Hazari et al.
Mutat Res 2017
Article in COPD
RA Sandhaus et al.
COPD 2013
Article in PLoS Genet
GA Thun et al.
PLoS Genet 2013
Article in Am J Respir Cell Mol Biol
R Busch et al.
Am J Respir Cell Mol Biol 2017
Article in BMC Genet
SM Lutz et al.
BMC Genet 2015
Article in Nat Genet
LV Wain et al.
Nat Genet 2017
Article in Proc Natl Acad Sci U S A
M Corley et al.
Proc Natl Acad Sci U S A 2017
Article in Am J Respir Crit Care Med
W Qiu et al.
Am J Respir Crit Care Med 2012
Article in Soz Praventivmed
BW Martin et al.
Soz Praventivmed 1997
Article in Soz Praventivmed
U Ackermann-Liebrich et al.
Soz Praventivmed 2005

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