Twin Study: Genotype-Dependent Epigenetic Factors Affecting Free Thyroxine Levels in the Normal Range

Abstract

Aim: To explore the clinical application of DNA methylation affecting thyroid function, we evaluated the association of DNA methylation with free thyroxine (FT4) and TSH measurements in monozygotic twins. Materials & methods: Discordant pairs for FT4 or TSH levels were examined for the relationship between the within-pair difference of each measurement and the DNA methylation levels using epigenome-wide association studies. The contribution of polymorphisms to the methylation sensitivity was also examined. Results: We found two CpG sites significantly associated with FT4 levels, and also some CpG sites showing significant differences in their methylation levels within FT4-discordant pairs depending on the polymorphism in EPHB2. Conclusion: The FT4 level may be associated with a combination of methylation and polymorphisms in the EPHB2 gene.

Graphical abstract

Keywords::

• EWAS
• FT4
• SNPs
• thyroxine
• TSH
• twin study

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/epi-2023-0372

Author contributions

Study conception and design were performed by S Yoshioka and M Watanabe; data collection was performed by M Watanabe, Y Arakawa and the Osaka Twin Research Group; statistical analysis was performed by S Yoshioka; analysis and interpretation of results were performed by M Watanabe, M Hasegawa, S Kato, H Hashimoto and S Mori; drafting of the article was performed by S Yoshioka, H Ueda and Y Arakawa; and supervision was provided by M Watanabe. All authors reviewed the results and edited and approved the final version of the manuscript.

Acknowledgments

The authors extend their appreciation to the Specially Appointed Researcher Kanako Akada (Center for Twin Research at Osaka University Graduate School of Medicine). The authors are also grateful to Beckman Coulter, Inc. (Tokyo, Japan) for their collaborative work.

Financial disclosure

The study was supported by JSPS KAKENHI (grant no. A19H040480) and University Grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

Language editing services were provided by Elsevier and were funded by JSPS KAKENHI (grant no. A19H040480).

Ethical conduct of research

In this study, written informed consent was obtained from all participants, and the study protocol was approved by the Ethics Committee of Osaka University (nos. 696 and 10209). The study was performed in accordance with the Declaration of Helsinki.

Additional information

Funding

The study was supported by JSPS KAKENHI (grant no. A19H040480) and University Grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.