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

TitleSERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts.
Publication TypeJournal Article
Year of Publication2018
AuthorsBeckmeyer-Borowko A, Imboden M, Rezwan FI, Wielscher M, Amaral AFS, Jeong A, Schaffner E, Auvinen J, Sebert S, Karhunen V, Bettschart R, Turk A, Pons M, Stolz D, Kronenberg F, Arathimos R, Sharp GC, Relton C, Henderson AJ, Jarvelin M-R, Jarvis D, Holloway JW, Probst-Hensch NM
JournalRespir Res
Date Published2018 Aug 22

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.

Alternate JournalRespir. Res.
PubMed ID30134983
PubMed Central IDPMC6103990
Grant ListR01 MH063706 / MH / NIMH NIH HHS / United States
MC_UU_12013_2, MC_UU_12013_5 and MC_UU_12013_8 / / University of Bristol (GB) /
No. 633212 / / Horizon 2020 Framework Programme /
R01 HL087679 / HL / NHLBI NIH HHS / United States
project grants 104781, 120315, 129269, 1114194, 24300796, 85547 / / Academy of Finland (FI) /
BB/I025751/1 and BB/I025263/1 / / UK Biotechnology and Biological Sciences Research Council /
90MR/10, 91AF/6 / / Ministère de la Santé (TN) /
/ / Wellcome Trust / United Kingdom
RL1 MH083268 / MH / NIMH NIH HHS / United States
grants no 33CS30148470/1&2, 33CSCO134276/1, 33CSCO108796, , 324730_135673, 3247BO104283, 3247BO104288, 3247BO104284, 3247065896, 3100059302, 3200052720, 3200042532, 4026028099, PMPDP3_129021/1, PMPDP3_141671/1 / / Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CH) /