Bingxuan Ren , Yun Chen , Jinjin Liu , Zheng Zhou , Yanhong He , Siyuan Wan , Yao Chen , Xianhao Wu , Mengxue Du , Haiyan Gao , Lixiang Liu , Hongmei Shen
{"title":"介导自噬体形成的基因的DNA甲基化有助于碘诱导的自身免疫性甲状腺炎:一项在中国不同碘水平地区进行的基于人群的研究","authors":"Bingxuan Ren , Yun Chen , Jinjin Liu , Zheng Zhou , Yanhong He , Siyuan Wan , Yao Chen , Xianhao Wu , Mengxue Du , Haiyan Gao , Lixiang Liu , Hongmei Shen","doi":"10.1016/j.ijheh.2025.114537","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><div>Autoimmune thyroiditis (AIT) results from a combination of genetic predispositions and environmental factors. This study aims to examine the methylation patterns of genes that mediate autophagosome formation (MAF) between AIT patients and controls from areas with different water iodine levels.</div></div><div><h3>Methods</h3><div>A protein-protein interaction (PPI) network was constructed to explore the interactions of autophagy-related genes (ARGs). The MCODE plugin in Cytoscape software identified two functional epigenetic modules. We included 176 AIT cases from regions with varying water iodine concentrations and matched controls at a 1:1 ratio. The MethylTarget™ assay was employed to assess DNA methylation changes in six MAF-related genes and analyzed the association between iodine levels and epigenetic modifications.</div></div><div><h3>Results</h3><div>Significant methylation differences were observed in 11 targets with 75 CpG sites on MAF-related genes between AIT patients and controls (<em>P</em> < 0.05). Methylation levels were generally lower in AIT patients. A negative correlation was found between the methylation status of PRKAB1_36 and urinary iodine concentration (UIC) (<em>r</em><sub><em>s</em></sub> = −0.208, <em>P</em> = 0.006). In iodine-fortification areas (IFA), AIT patients exhibited significantly higher mRNA expression levels of six MAF-related genes in whole blood compared to controls (<em>P</em> < 0.05).</div></div><div><h3>Conclusion</h3><div>Environmental water iodine concentration influences the DNA methylation status of MAF-related genes. Hypomethylated targets and sites in these genes were identified, and the relative mRNA expression levels of these genes were significantly increased in AIT cases from regions with a history of prolonged iodine deficiency followed by iodine supplementation.</div></div>","PeriodicalId":13994,"journal":{"name":"International journal of hygiene and environmental health","volume":"265 ","pages":"Article 114537"},"PeriodicalIF":4.5000,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"DNA methylation of genes that mediate autophagosome formation contributes to iodine-induced autoimmune thyroiditis: A population-based study conducted at regions with different iodine levels in China\",\"authors\":\"Bingxuan Ren , Yun Chen , Jinjin Liu , Zheng Zhou , Yanhong He , Siyuan Wan , Yao Chen , Xianhao Wu , Mengxue Du , Haiyan Gao , Lixiang Liu , Hongmei Shen\",\"doi\":\"10.1016/j.ijheh.2025.114537\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><div>Autoimmune thyroiditis (AIT) results from a combination of genetic predispositions and environmental factors. This study aims to examine the methylation patterns of genes that mediate autophagosome formation (MAF) between AIT patients and controls from areas with different water iodine levels.</div></div><div><h3>Methods</h3><div>A protein-protein interaction (PPI) network was constructed to explore the interactions of autophagy-related genes (ARGs). The MCODE plugin in Cytoscape software identified two functional epigenetic modules. We included 176 AIT cases from regions with varying water iodine concentrations and matched controls at a 1:1 ratio. The MethylTarget™ assay was employed to assess DNA methylation changes in six MAF-related genes and analyzed the association between iodine levels and epigenetic modifications.</div></div><div><h3>Results</h3><div>Significant methylation differences were observed in 11 targets with 75 CpG sites on MAF-related genes between AIT patients and controls (<em>P</em> < 0.05). Methylation levels were generally lower in AIT patients. A negative correlation was found between the methylation status of PRKAB1_36 and urinary iodine concentration (UIC) (<em>r</em><sub><em>s</em></sub> = −0.208, <em>P</em> = 0.006). In iodine-fortification areas (IFA), AIT patients exhibited significantly higher mRNA expression levels of six MAF-related genes in whole blood compared to controls (<em>P</em> < 0.05).</div></div><div><h3>Conclusion</h3><div>Environmental water iodine concentration influences the DNA methylation status of MAF-related genes. Hypomethylated targets and sites in these genes were identified, and the relative mRNA expression levels of these genes were significantly increased in AIT cases from regions with a history of prolonged iodine deficiency followed by iodine supplementation.</div></div>\",\"PeriodicalId\":13994,\"journal\":{\"name\":\"International journal of hygiene and environmental health\",\"volume\":\"265 \",\"pages\":\"Article 114537\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-02-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International journal of hygiene and environmental health\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1438463925000197\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International journal of hygiene and environmental health","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1438463925000197","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
摘要
目的自身免疫性甲状腺炎(AIT)是遗传易感性和环境因素共同作用的结果。本研究旨在研究AIT患者和来自不同水碘水平地区的对照组之间介导自噬体形成(MAF)的基因甲基化模式。方法构建蛋白-蛋白相互作用(PPI)网络,探讨自噬相关基因(ARGs)的相互作用。Cytoscape软件中的MCODE插件鉴定了两个功能性表观遗传模块。我们纳入了176例来自不同水碘浓度地区的AIT病例,并以1:1的比例匹配对照。MethylTarget™检测用于评估6个maf相关基因的DNA甲基化变化,并分析碘水平与表观遗传修饰之间的关系。结果AIT患者与对照组在maf相关基因的75个CpG位点的11个靶点上存在显著的甲基化差异(P <;0.05)。AIT患者的甲基化水平普遍较低。PRKAB1_36甲基化状态与尿碘浓度(UIC)呈负相关(rs = - 0.208, P = 0.006)。在碘强化区(IFA), AIT患者的全血中6个与maf相关的基因的mRNA表达水平显著高于对照组(P <;0.05)。结论环境水碘浓度影响maf相关基因的DNA甲基化状态。这些基因的低甲基化靶点和位点被鉴定出来,这些基因的相对mRNA表达水平在长期缺碘后补充碘的地区的AIT病例中显著升高。
DNA methylation of genes that mediate autophagosome formation contributes to iodine-induced autoimmune thyroiditis: A population-based study conducted at regions with different iodine levels in China
Purpose
Autoimmune thyroiditis (AIT) results from a combination of genetic predispositions and environmental factors. This study aims to examine the methylation patterns of genes that mediate autophagosome formation (MAF) between AIT patients and controls from areas with different water iodine levels.
Methods
A protein-protein interaction (PPI) network was constructed to explore the interactions of autophagy-related genes (ARGs). The MCODE plugin in Cytoscape software identified two functional epigenetic modules. We included 176 AIT cases from regions with varying water iodine concentrations and matched controls at a 1:1 ratio. The MethylTarget™ assay was employed to assess DNA methylation changes in six MAF-related genes and analyzed the association between iodine levels and epigenetic modifications.
Results
Significant methylation differences were observed in 11 targets with 75 CpG sites on MAF-related genes between AIT patients and controls (P < 0.05). Methylation levels were generally lower in AIT patients. A negative correlation was found between the methylation status of PRKAB1_36 and urinary iodine concentration (UIC) (rs = −0.208, P = 0.006). In iodine-fortification areas (IFA), AIT patients exhibited significantly higher mRNA expression levels of six MAF-related genes in whole blood compared to controls (P < 0.05).
Conclusion
Environmental water iodine concentration influences the DNA methylation status of MAF-related genes. Hypomethylated targets and sites in these genes were identified, and the relative mRNA expression levels of these genes were significantly increased in AIT cases from regions with a history of prolonged iodine deficiency followed by iodine supplementation.
期刊介绍:
The International Journal of Hygiene and Environmental Health serves as a multidisciplinary forum for original reports on exposure assessment and the reactions to and consequences of human exposure to the biological, chemical, and physical environment. Research reports, short communications, reviews, scientific comments, technical notes, and editorials will be peer-reviewed before acceptance for publication. Priority will be given to articles on epidemiological aspects of environmental toxicology, health risk assessments, susceptible (sub) populations, sanitation and clean water, human biomonitoring, environmental medicine, and public health aspects of exposure-related outcomes.