Exposure to air pollution increases susceptibility to ulcerative colitis through epigenetic alterations in CXCR2 and MHC class III regionResearch in context
Summary: Background: This study aims to confirm the associations of air pollution with ulcerative colitis (UC) and Crohn's disease (CD); to explore interactions with genetics and lifestyle; and to characterize potential epigenetic mechanisms. Methods: We identified over 450,000 individuals fro...
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Elsevier
2024-12-01
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| author | Jie Chen Han Zhang Tian Fu Jianhui Zhao Jan Krzysztof Nowak Rahul Kalla Judith Wellens Shuai Yuan Alexandra Noble Nicholas T. Ventham Malcolm G. Dunlop Jonas Halfvarson Ren Mao Evropi Theodoratou Jack Satsangi Xue Li |
| author_facet | Jie Chen Han Zhang Tian Fu Jianhui Zhao Jan Krzysztof Nowak Rahul Kalla Judith Wellens Shuai Yuan Alexandra Noble Nicholas T. Ventham Malcolm G. Dunlop Jonas Halfvarson Ren Mao Evropi Theodoratou Jack Satsangi Xue Li |
| author_sort | Jie Chen |
| collection | DOAJ |
| description | Summary: Background: This study aims to confirm the associations of air pollution with ulcerative colitis (UC) and Crohn's disease (CD); to explore interactions with genetics and lifestyle; and to characterize potential epigenetic mechanisms. Methods: We identified over 450,000 individuals from the UK Biobank and investigated the relationship between air pollution and incident inflammatory bowel disease (IBD). Cox regression was utilized to calculate hazard ratios (HRs), while also exploring potential interactions with genetics and lifestyle factors. Additionally, we conducted epigenetic Mendelian randomization (MR) analyses to examine the association between air pollution-related DNA methylation and UC. Finally, our findings were validated through genome-wide DNA methylation analysis of UC, as well as co-localization and gene expression analyses. Findings: Higher exposures to NOx (HR = 1.20, 95% CI 1.05–1.38), NO2 (HR = 1.19, 95% CI = 1.03–1.36), PM2.5 (HR = 1.19, 95% CI = 1.05–1.36) and combined air pollution score (HR = 1.26, 95% CI = 1.11–1.45) were associated with incident UC but not CD. Interactions with genetic risk score and lifestyle were observed. In MR analysis, we found five and 22 methylated CpG sites related to PM2.5 and NO2 exposure to be significantly associated with UC. DNA methylation alterations at CXCR2 and sites within the MHC class III region, were validated in genome-wide DNA methylation analysis, co-localization analysis and analysis of colonic tissue. Interpretation: We report a potential causal association between air pollution and UC, modified by lifestyle and genetic influences. Biological pathways implicated include epigenetic alterations in key genetic loci, including CXCR2 and susceptible loci within MHC class III region. Funding: Xue Li was supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and the National Nature Science Foundation of China (No. 82204019). ET was supported by the CRUK Career Development Fellowship (C31250/A22804) and the Research Foundation Flanders (FWO). JW was supported by Belgium by a PhD Fellowship strategic basic research (SB) grant (1S06023N). JKN was supported by the National Science Center, Poland (No. 2020/39/D/NZ5/02720). The IBD Character was supported by the European Union's Seventh Framework Programme [FP7] grant IBD Character (No. 2858546). |
| format | Article |
| id | doaj-art-2f7b2d8722784ab88ccf8c0ceb2b28a7 |
| institution | Kabale University |
| issn | 2352-3964 |
| language | English |
| publishDate | 2024-12-01 |
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| series | EBioMedicine |
| spelling | doaj-art-2f7b2d8722784ab88ccf8c0ceb2b28a72024-11-14T04:32:32ZengElsevierEBioMedicine2352-39642024-12-01110105443Exposure to air pollution increases susceptibility to ulcerative colitis through epigenetic alterations in CXCR2 and MHC class III regionResearch in contextJie Chen0Han Zhang1Tian Fu2Jianhui Zhao3Jan Krzysztof Nowak4Rahul Kalla5Judith Wellens6Shuai Yuan7Alexandra Noble8Nicholas T. Ventham9Malcolm G. Dunlop10Jonas Halfvarson11Ren Mao12Evropi Theodoratou13Jack Satsangi14Xue Li15The Second Affiliated Hospital and School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, ChinaThe Second Affiliated Hospital and School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaThe Second Affiliated Hospital and School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China; Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Westlake University Medical College, Hangzhou, ChinaThe Second Affiliated Hospital and School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, 60572, Poznan, PolandMedical Research Council Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United KingdomKU Leuven Department of Chronic Diseases and Metabolism, Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven, Belgium; Translational Gastro-Intestinal Unit, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UKUnit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SwedenTranslational Gastro-Intestinal Unit, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UKMedical Research Council Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United KingdomCancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UKDepartment of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, SwedenDepartment of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaCancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom; Corresponding author. Cancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.Translational Gastro-Intestinal Unit, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK; Corresponding author.The Second Affiliated Hospital and School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Corresponding author.Summary: Background: This study aims to confirm the associations of air pollution with ulcerative colitis (UC) and Crohn's disease (CD); to explore interactions with genetics and lifestyle; and to characterize potential epigenetic mechanisms. Methods: We identified over 450,000 individuals from the UK Biobank and investigated the relationship between air pollution and incident inflammatory bowel disease (IBD). Cox regression was utilized to calculate hazard ratios (HRs), while also exploring potential interactions with genetics and lifestyle factors. Additionally, we conducted epigenetic Mendelian randomization (MR) analyses to examine the association between air pollution-related DNA methylation and UC. Finally, our findings were validated through genome-wide DNA methylation analysis of UC, as well as co-localization and gene expression analyses. Findings: Higher exposures to NOx (HR = 1.20, 95% CI 1.05–1.38), NO2 (HR = 1.19, 95% CI = 1.03–1.36), PM2.5 (HR = 1.19, 95% CI = 1.05–1.36) and combined air pollution score (HR = 1.26, 95% CI = 1.11–1.45) were associated with incident UC but not CD. Interactions with genetic risk score and lifestyle were observed. In MR analysis, we found five and 22 methylated CpG sites related to PM2.5 and NO2 exposure to be significantly associated with UC. DNA methylation alterations at CXCR2 and sites within the MHC class III region, were validated in genome-wide DNA methylation analysis, co-localization analysis and analysis of colonic tissue. Interpretation: We report a potential causal association between air pollution and UC, modified by lifestyle and genetic influences. Biological pathways implicated include epigenetic alterations in key genetic loci, including CXCR2 and susceptible loci within MHC class III region. Funding: Xue Li was supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and the National Nature Science Foundation of China (No. 82204019). ET was supported by the CRUK Career Development Fellowship (C31250/A22804) and the Research Foundation Flanders (FWO). JW was supported by Belgium by a PhD Fellowship strategic basic research (SB) grant (1S06023N). JKN was supported by the National Science Center, Poland (No. 2020/39/D/NZ5/02720). The IBD Character was supported by the European Union's Seventh Framework Programme [FP7] grant IBD Character (No. 2858546).http://www.sciencedirect.com/science/article/pii/S2352396424004791Inflammatory bowel diseaseAir pollutionDNA methylationMendelian randomizationMHC III region |
| spellingShingle | Jie Chen Han Zhang Tian Fu Jianhui Zhao Jan Krzysztof Nowak Rahul Kalla Judith Wellens Shuai Yuan Alexandra Noble Nicholas T. Ventham Malcolm G. Dunlop Jonas Halfvarson Ren Mao Evropi Theodoratou Jack Satsangi Xue Li Exposure to air pollution increases susceptibility to ulcerative colitis through epigenetic alterations in CXCR2 and MHC class III regionResearch in context EBioMedicine Inflammatory bowel disease Air pollution DNA methylation Mendelian randomization MHC III region |
| title | Exposure to air pollution increases susceptibility to ulcerative colitis through epigenetic alterations in CXCR2 and MHC class III regionResearch in context |
| title_full | Exposure to air pollution increases susceptibility to ulcerative colitis through epigenetic alterations in CXCR2 and MHC class III regionResearch in context |
| title_fullStr | Exposure to air pollution increases susceptibility to ulcerative colitis through epigenetic alterations in CXCR2 and MHC class III regionResearch in context |
| title_full_unstemmed | Exposure to air pollution increases susceptibility to ulcerative colitis through epigenetic alterations in CXCR2 and MHC class III regionResearch in context |
| title_short | Exposure to air pollution increases susceptibility to ulcerative colitis through epigenetic alterations in CXCR2 and MHC class III regionResearch in context |
| title_sort | exposure to air pollution increases susceptibility to ulcerative colitis through epigenetic alterations in cxcr2 and mhc class iii regionresearch in context |
| topic | Inflammatory bowel disease Air pollution DNA methylation Mendelian randomization MHC III region |
| url | http://www.sciencedirect.com/science/article/pii/S2352396424004791 |
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