Genome-wide methylation analysis of pre-pregnancy women in hypothyroidism

Abstract

Background

Hypothyroidism is a systemic metabolic deficiency syndrome caused by a deficiency in thyroid hormone or a decrease in the action of thyroid hormones. It has a high incidence among women of child-bearing age, and pregnant women with hypothyroidism may have a higher risk of birth defects.

Objective

To explore the specific biological mechanism affecting the occurrence of hypothyroidism.

Methods

This study determined key molecules by comparing and analyzing the difference in methylation levels between pre-pregnancy women and normal controls using the Illumina Infinium MethylationEPIC BeadChip.

Results

3493 Differential methylation positions (DMPs) related genes and 47 differentially methylated regions (DMRs) related genes were found between the Hypothyroidism group and the control group. Among them, miR-21 has been found to be closely related to thyroid hormone regulation. The results of enrichment analysis showed that the DMPs or DMRs-related genes are both significantly enriched in human T-cell leukemia virus 1 infection, osteoclast differentiation and sphingolipid signaling pathway, which were also closely related to the occurrence and development of hypothyroidism. In addition, the combined analysis of CNVs and DMRs showed that significant differences occurred near the regions of 16 M bp in chromosome 1 between the two groups, and the genes involved in these regions included NDUFS2, FCER1G and SHC1.

Conclusion

This work screened molecular markers and key signaling pathways that are involved in the development of hypothyroidism in pre-pregnancy women, which may provide new targets for the research and diagnosis of hypothyroidism in the future.

Keywords:

• Hypothyroidism
• Pre-pregnancy
• MiR-21
• NDUFS2
• Human T-cell leukemia virus 1

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Additional information

Funding

This work was supported by grants from Key Research Project of the Nature Scientific Foundation of Hubei Province, China [Grant No.: 2017CFB254] and Scientific Research Foundation of Wuhan City, China [Grant No.: WX17Q24].