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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

Beckmeyer-Borowko, Anna and Imboden, Medea and Rezwan, Faisal I. and Wielscher, Matthias and Amaral, Andre F. S. and Jeong, Ayoung and Schaffner, Emmanuel and Auvinen, Juha and Sebert, Sylvain and Karhunen, Ville and Bettschart, Robert and Turk, Alexander and Pons, Marco and Stolz, Daiana and Kronenberg, Florian and Arathimos, Ryan and Sharp, Gemma C. and Relton, Caroline and Henderson, Alexander J. and Jarvelin, Marjo-Riitta and Jarvis, Deborah and 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. p. 156.

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Abstract

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.; 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.; Methylation at cg08257009 in the SERPINA gene cluster, located 32 kb downstream of SERPINA1, not annotated to a gene, was associated with FEV; 1; /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.; 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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Beckmeyer-Borowko, Anna and Imboden, Medea and Jeong, Ayoung and Schaffner, Emmanuel and Probst-Hensch, Nicole
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:BioMed Central
ISSN:1465-9921
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:11 Sep 2018 13:20
Deposited On:11 Sep 2018 13:20

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