Twin study: genotype-dependent epigenetic factors affecting free thyroxine levels in the normal range.

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.