From DIO2 Genotype to Personalized Medication
by Jihong Jung
Abstract – Hypothyroidism is a syndrome in which the metabolic process of the entire body is degraded due to a lack of thyroid hormones. The single nucleotide polymorphism (SNP) information from the DIO2 gene found in the patient's genome is currently used in combination therapy: a treatment for hypothyroidism by providing patients with levothyroxine and liothyronine together. In patients with rs225014 (T→C) transition in DIO2, the conversion from prohormone thyroxine (T4) to bioactive thyroid hormone (T3) proceeds inefficiently even if the level of T4 is increased through Levothyroxine (LT4). However, there is a lack of information to explain how the SNP of DIO2 is linked with the effectiveness of the treatment, and some findings are incomplete and conflicting. In this study, we analyzed the cellular localization of the DIO2 gene, and investigated the tissue-specific gene expression of DIO2 in our body organs. We also conducted a gene network analysis of DIO2 to find the closely related genes to DIO2. Our result shows that the DIO2 gene is closely associated with eight proteins that function as Ubiquitindependent proteins. Thus, this study investigated for the first time that DIO2 functions as a homeostasis regulator for thyroid hormones and is closely involved in the proteolytic regulatory system by ubiquitin. The findings provide more information on DIO2 gene function, which can be applied to the development of personalized treatments for hypothyroidism, suggesting that the drugs can be prescribed more precisely and accurately.