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. 2021 Mar 3;11:5022. doi: 10.1038/s41598-021-83185-1

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Differential DNA methylation patterns of the IRFD1, TIGIT, CysLTR1, ADORA2B, CCDC88C, ZNF323, and MPV17L, and PTPRN2 genes at cross sectional or longitudinal levels in the validation cohort. (A) DNA methylation levels of the CYSLTR1 gene promoter region (+ 348 CpG site) were positively correlated with post-BD FEV1%predicted value. (B) DNA methylation levels of the CCDC88C gene body (+ 125,722 CpG site) were positively correlated with post-BD FEV1%predicted value. (C) DNA methylation levels of the ADORA2B gene body (+ 1339 CpG site) were positively correlated with post-BD FEV1%predicted value. (D) DNA methylation levels of the TIGIT gene promoter region (− 172 CpG site) were negatively correlated with post-BD FEV1%predicted value. (E) DNA methylation levels of the IFRD1 gene promoter region (− 515 CpG site) were decreased in all the COPD patients with frequent exacerbation versus those without frequent exacerbation, and (F) negatively correlated with the number of exacerbations in the past one year. (G) DNA methylation levels of the ZNF323 gene promoter region (− 296 CpG site) were elevated after 1-year follow-up in COPD patients with rapid lung function decline versus that at enrollment. (H) DNA methylation levels of the MPV17L gene (+ 194 CpG site) were elevated after 1-year follow-up in COPD patients with rapid lung function decline versus that at enrollment. (I) DNA methylation levels of the MPV17L gene (+ 194 CpG site) at visit 1 were negatively correlated with the difference in FEV1% predicted values between visit 2 and visit 1. (J) DNA methylation levels over + 10,015 CpG site of the PTPRN2 gene were reduced after 1-year follow-up in COPD patients with frequent exacerbation versus that at enrollment.