biostudies-literatureBeckmeyer-Borowko AMinistère de la Santé (TN)Swiss National Science FoundationHorizon 2020 Framework ProgrammeUniversity of Bristol (GB)Medical Research CouncilNHLBI NIH HHSNIMH NIH HHSAcademy of Finland (FI)Wellcome TrustBiotechnology and Biological Sciences Research Council156https://www.ebi.ac.uk/biostudies/studies/S-EPMC6103990biostudies-literatureUnknown19(1)<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.Respiratory researchSERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts.PMC6103990R01 MH063706WT088806G9815508BB/I025263/1No. 633212WT084703MAMR/M022501/1R01 HL087679BB/I025751/1 and BB/I025263/1MC_UU_12013/2grants no 33CS30148470/1&2, 33CSCO134276/1, 33CSCO108796, , 324730_135673, 3247BO104283, 3247BO104288, 3247BO104284, 3247065896, 3100059302, 3200052720, 3200042532, 4026028099, PMPDP3_129021/1, PMPDP3_141671/1RL1 MH083268project grants 104781, 120315, 129269, 1114194, 24300796, 85547grants no 33CS30148470/1&amp;2, 33CSCO134276/1, 33CSCO108796, , 324730_135673, 3247BO104283, 3247BO104288, 3247BO104284, 3247065896, 3100059302, 3200052720, 3200042532, 4026028099, PMPDP3_129021/1, PMPDP3_141671/1MC_UU_12013_2, MC_UU_12013_5 and MC_UU_12013_890MR/10, 91AF/6090532/Z/09/ZBB/I025751/1MC_PC_15018MC_UU_00011/5Karhunen VPons MBeckmeyer-Borowko ASchaffner EWielscher MBettschart RJarvis DTurk AStolz DImboden MAuvinen JRelton CKronenberg FJarvelin MRRezwan FIHenderson AJJeong AProbst-Hensch NMArathimos RSharp GCSebert SHolloway JWAmaral AFSfalseSERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.2018-01-01T00:00:00Z2018 Aug2024-11-13T08:18:10.409Z2019-03-26T23:53:34ZS-EPMC61039903013498310.1186/s12931-018-0850-8