Genome‐wide DNA methylation analysis of Hashimoto's thyroiditis during pregnancy

Abstract

Hashimoto's thyroiditis (HT) during pregnancy is usually accompanied by an elevation of thyroid-stimulating hormone and a reduction of serum free thyroxine during gestation, which may lead to abortion, preterm delivery, and reduced intellectual function of the offspring. Epigenetic alterations may provide important insights into genetic-environmental interactions in HT. Here, we examined global DNA methylation patterns in patients with HT during pregnancy. DNA was extracted from 13 women with HT during pregnancy (HTDP) and 8 healthy pregnant women as a control group. Genome-wide methylation was detected with the use of an Illumina Human Methylation 850K Beadchip. A total of 652 differentially methylated positions (DMPs) and 27 differentially methylated regions (DMRs) were identified between the HTDP and control groups. GO analysis revealed that DMPs were significantly enriched in 540 GO terms, which included regulation of the differentiation of keratinocytes, T-helper cell differentiation, and alpha-beta T cell differentiation. Moreover, significant enrichment of KEGG pathways of the DMPs included mucin type O-glycan biosynthesis, focal adhesion, and the insulin signaling pathway. The GO items associated with DMRs included muscle cell proliferation, response to biotic stimulus, anatomical structure formation involved in morphogenesis, and genes primarily involved in the FoxO signaling pathway. Finally, the DTNA gene was identified as the seed gene of functional epigenetic modules. In summary, the DNA methylation pattern of the HTDP group was distinct from that of the control group, and thus changes in DNA methylation may influence the development of HT by regulation of the autoimmunity process.

Pathogenesis Markers of Hashimoto's Disease—A Mini Review

“…Tregs consist mainly of CD4 + , CD25 + , and FOXP3, the first two markers of immune cells and FOXP3 an autoantigen, all of which are important components of the immune response [42]. SIRT1-mediated aberrant FOXP3 acetylation activates Tregs, and therefore HT can be treated by modulating SIRT1 [43]. CD4 + CD25 + +FOXP3+ Treg subgroups play an important role in autoimmune diseases.…”

Whole genome and transcriptome sequencing in neuromuscular disorders: a diagnostic and health economic analysis

“…However, the main challenge lies in the prioritization and interpretation of variants for clinical application. In recent years, the integration of RNA sequencing (RNA-seq) into the diagnosis of genetic diseases has improved the diagnostic yield by 7.5%-35% [15, 16] in patients with negative WES results. RNA-seq offers valuable insights into the biological impact of candidate variants.…”

“…Additionally, proteomics and methylation analyses have shown promise in certain NMD disorders, such as Duchenne Muscular Dystrophy (DMD) [13, 14], Myasthenia Gravis [15], and Facio-Scapulo-Humeral Dystrophy (FSHD) [16]. These analyses provide proteomic and epigenetic signatures, enabling accurate diagnosis in some patients.…”