Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditis

Zheng Zhou; Jinjin Liu; Yun Chen; Bingxuan Ren; Siyuan Wan; Yao Chen; Yanhong He; Qiuyang Wei; Haiyan Gao; Lixiang Liu; Hongmei Shen

doi:10.3389/fendo.2023.1259903

Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditis

Front Endocrinol (Lausanne). 2023 Nov 24:14:1259903. doi: 10.3389/fendo.2023.1259903. eCollection 2023.

Authors

Zheng Zhou^{1

2

3}, Jinjin Liu^{1

2

3}, Yun Chen^{1

2

3}, Bingxuan Ren^{1

2

3}, Siyuan Wan⁴, Yao Chen^{1

2

3}, Yanhong He^{1

2

3}, Qiuyang Wei^{5

6}, Haiyan Gao^{1

2

3

7}, Lixiang Liu^{1

2

3}, Hongmei Shen^{1

2

3}

Affiliations

¹ Disorders Control, Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China.
² Key Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, China.
³ Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang, China.
⁴ Department of Preventive Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
⁵ First Clinical Medical Department, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.
⁶ Second Department of Endocrinology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China.
⁷ Department of Clinical Laboratory, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, China.

Abstract

Background: Hashimoto 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.

Method: Using 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.

Results: The 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.

Conclusion: This 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.

Keywords: DNA methylation; Hashimoto thyroiditis; SLFN12; autoimmune endocrinopathies; epigenetics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA Methylation*
Epigenesis, Genetic
Epigenomics
Hashimoto Disease* / genetics
Humans
Protein Processing, Post-Translational

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by grants from the National Natural Science Foundation of China (82073490).