Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditis
BackgroundHashimoto thyroiditis (HT), a prevalent autoimmune disorder, is not yet thoroughly understood, especially when it comes to the influence of epigenetics in its pathogenesis. The primary goal of this research was to probe the DNAm profile across the genome in the whole blood derived from pat...
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Frontiers Media S.A.
2023-11-01
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| author | Zheng Zhou Zheng Zhou Zheng Zhou Jinjin Liu Jinjin Liu Jinjin Liu Yun Chen Yun Chen Yun Chen Bingxuan Ren Bingxuan Ren Bingxuan Ren Siyuan Wan Yao Chen Yao Chen Yao Chen Yanhong He Yanhong He Yanhong He Qiuyang Wei Qiuyang Wei Haiyan Gao Haiyan Gao Haiyan Gao Haiyan Gao Lixiang Liu Lixiang Liu Lixiang Liu Hongmei Shen Hongmei Shen Hongmei Shen |
| author_facet | Zheng Zhou Zheng Zhou Zheng Zhou Jinjin Liu Jinjin Liu Jinjin Liu Yun Chen Yun Chen Yun Chen Bingxuan Ren Bingxuan Ren Bingxuan Ren Siyuan Wan Yao Chen Yao Chen Yao Chen Yanhong He Yanhong He Yanhong He Qiuyang Wei Qiuyang Wei Haiyan Gao Haiyan Gao Haiyan Gao Haiyan Gao Lixiang Liu Lixiang Liu Lixiang Liu Hongmei Shen Hongmei Shen Hongmei Shen |
| author_sort | Zheng Zhou |
| collection | DOAJ |
| description | BackgroundHashimoto thyroiditis (HT), a prevalent autoimmune disorder, is not yet thoroughly understood, especially when it comes to the influence of epigenetics in its pathogenesis. The primary goal of this research was to probe the DNAm profile across the genome in the whole blood derived from patients suffering from HT.MethodUsing the Illumina 850K BeadChip, we conducted a genome-wide DNAm assessment on 10 matched pairs of HT sufferers and healthy individuals. Genes with differential methylation (DMGs) were identified and underwent functional annotation via the databases of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The transcriptional significance of potential epigenetic biomarker genes was corroborated through qRT-PCR.ResultsThe DNAm profiling across the genome indicated an overall reduction in methylation in HT subjects in comparison with their healthy counterparts. We detected 283 DMPs (adjusted P < 0.05 and |Δβ| > 0.1), among which 152 exhibited hypomethylation and 131 demonstrated hypermethylation. Further analysis exposed a noteworthy concentration of hypermethylated DMPs in the 3´UTR, North Shore, and CpG islands, while there was a significant decrease in the Open Sea (all P < 0.001). The 283 DMPs were broadly distributed from chromosome 1 to 22, with chromosome 6 harboring the most DMPs (n = 51) and chromosome 12 carrying the most DMGs (n = 15). The SLFN12 gene, which presented with extreme hypomethylation in its promoter DMPs among HT patients, was identified as the epigenetic marker gene. Consequently, the SLFN12 mRNA expression was markedly upregulated in HT, displaying a negative relationship with its methylation levels. The area under curve (AUC) value for the SLFN12 gene among HT patients was 0.85 (sensitivity: 0.7, specificity: 0.7), a significant difference compared with healthy controls. The methylation levels of all DMPs in SLFN12 gene were negatively correlated with TSH and one CpG site (cg24470734) was positively assocciated with FT4.ConclusionThis investigation presents an initial comprehensive DNAm blueprint for individuals with HT, which permits clear differentiation between HT subjects and normal controls through an epigenetic lens. The SLFN12 gene plays a pivotal role in the onset of HT, suggesting that the methylation status of this gene could serve as a potential epigenetic indicator for HT. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-14fabc2a2e904184b9269c6a310ce9d02023-11-24T13:37:18ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-11-011410.3389/fendo.2023.12599031259903Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditisZheng Zhou0Zheng Zhou1Zheng Zhou2Jinjin Liu3Jinjin Liu4Jinjin Liu5Yun Chen6Yun Chen7Yun Chen8Bingxuan Ren9Bingxuan Ren10Bingxuan Ren11Siyuan Wan12Yao Chen13Yao Chen14Yao Chen15Yanhong He16Yanhong He17Yanhong He18Qiuyang Wei19Qiuyang Wei20Haiyan Gao21Haiyan Gao22Haiyan Gao23Haiyan Gao24Lixiang Liu25Lixiang Liu26Lixiang Liu27Hongmei Shen28Hongmei Shen29Hongmei Shen30Disorders Control, Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, ChinaKey Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, ChinaHeilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang, ChinaDisorders Control, Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, ChinaKey Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, ChinaHeilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang, ChinaDisorders Control, Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, ChinaKey Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, ChinaHeilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang, ChinaDisorders Control, Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, ChinaKey Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, ChinaHeilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang, ChinaDepartment of Preventive Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang, ChinaDisorders Control, Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, ChinaKey Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, ChinaHeilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang, ChinaDisorders Control, Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, ChinaKey Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, ChinaHeilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang, ChinaFirst Clinical Medical Department, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, ChinaSecond Department of Endocrinology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, ChinaDisorders Control, Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, ChinaKey Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, ChinaHeilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang, ChinaDepartment of Clinical Laboratory, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, ChinaDisorders Control, Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, ChinaKey Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, ChinaHeilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang, ChinaDisorders Control, Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, ChinaKey Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, ChinaHeilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang, ChinaBackgroundHashimoto thyroiditis (HT), a prevalent autoimmune disorder, is not yet thoroughly understood, especially when it comes to the influence of epigenetics in its pathogenesis. The primary goal of this research was to probe the DNAm profile across the genome in the whole blood derived from patients suffering from HT.MethodUsing the Illumina 850K BeadChip, we conducted a genome-wide DNAm assessment on 10 matched pairs of HT sufferers and healthy individuals. Genes with differential methylation (DMGs) were identified and underwent functional annotation via the databases of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The transcriptional significance of potential epigenetic biomarker genes was corroborated through qRT-PCR.ResultsThe DNAm profiling across the genome indicated an overall reduction in methylation in HT subjects in comparison with their healthy counterparts. We detected 283 DMPs (adjusted P < 0.05 and |Δβ| > 0.1), among which 152 exhibited hypomethylation and 131 demonstrated hypermethylation. Further analysis exposed a noteworthy concentration of hypermethylated DMPs in the 3´UTR, North Shore, and CpG islands, while there was a significant decrease in the Open Sea (all P < 0.001). The 283 DMPs were broadly distributed from chromosome 1 to 22, with chromosome 6 harboring the most DMPs (n = 51) and chromosome 12 carrying the most DMGs (n = 15). The SLFN12 gene, which presented with extreme hypomethylation in its promoter DMPs among HT patients, was identified as the epigenetic marker gene. Consequently, the SLFN12 mRNA expression was markedly upregulated in HT, displaying a negative relationship with its methylation levels. The area under curve (AUC) value for the SLFN12 gene among HT patients was 0.85 (sensitivity: 0.7, specificity: 0.7), a significant difference compared with healthy controls. The methylation levels of all DMPs in SLFN12 gene were negatively correlated with TSH and one CpG site (cg24470734) was positively assocciated with FT4.ConclusionThis investigation presents an initial comprehensive DNAm blueprint for individuals with HT, which permits clear differentiation between HT subjects and normal controls through an epigenetic lens. The SLFN12 gene plays a pivotal role in the onset of HT, suggesting that the methylation status of this gene could serve as a potential epigenetic indicator for HT.https://www.frontiersin.org/articles/10.3389/fendo.2023.1259903/fullHashimoto thyroiditisDNA methylationepigeneticsautoimmune endocrinopathiesSLFN12 |
| spellingShingle | Zheng Zhou Zheng Zhou Zheng Zhou Jinjin Liu Jinjin Liu Jinjin Liu Yun Chen Yun Chen Yun Chen Bingxuan Ren Bingxuan Ren Bingxuan Ren Siyuan Wan Yao Chen Yao Chen Yao Chen Yanhong He Yanhong He Yanhong He Qiuyang Wei Qiuyang Wei Haiyan Gao Haiyan Gao Haiyan Gao Haiyan Gao Lixiang Liu Lixiang Liu Lixiang Liu Hongmei Shen Hongmei Shen Hongmei Shen Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditis Frontiers in Endocrinology Hashimoto thyroiditis DNA methylation epigenetics autoimmune endocrinopathies SLFN12 |
| title | Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditis |
| title_full | Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditis |
| title_fullStr | Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditis |
| title_full_unstemmed | Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditis |
| title_short | Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditis |
| title_sort | genome wide dna methylation pattern in whole blood of patients with hashimoto thyroiditis |
| topic | Hashimoto thyroiditis DNA methylation epigenetics autoimmune endocrinopathies SLFN12 |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1259903/full |
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