Association between genetic polymorphism and levothyroxine bioavailability in hypothyroid patients

• Published in: ENDOCRINE JOURNAL 2018, Vol.65(3), pp.317-323
• Main Authors: Arici, Merve, Oztas, Ezgi, Yanar, Fatih, Aksakal, Nihat, Ozcinar, Beyza, Ozhan, Gul
• Format: Article
• Language: English
• Subjects: Bioavailability; Biological Availability; DNA-Binding Proteins - genetics; Energy metabolism; Female; Gene polymorphism; Genetic polymorphism; Glucuronosyltransferase - genetics; Hormones; Humans; Hypothyroid; Hypothyroidism; Hypothyroidism - blood; Hypothyroidism - drug therapy; Hypothyroidism - genetics; Iodide Peroxidase - genetics; Iodothyronine Deiodinase Type II; Levothyroxine; Male; Metabolism; Middle Aged; Oral administration; Patients; Pharmacogenetics; Polymorphism, Single Nucleotide; Receptors, Thyroid Hormone - genetics; Receptors, Thyrotropin - genetics; Thyroid Function Tests; Thyroid gland; Thyroid hormones; Thyroid Hormones - blood; Thyroid-stimulating hormone; Thyroid-stimulating hormone receptors; Thyroxine; Thyroxine - pharmacokinetics; Thyroxine - therapeutic use; Toxicity; Triiodothyronine
• ISSN: 0918-8959; 1348-4540
• DOI: 10.1507/endocrj.EJ17-0162

Thyroid hormones play a vital role in the human body for growth and differentiation, regulation of energy metabolism, and physiological function. Hypothyroidism is a common endocrine disorder, which generally results from diminished normal circulating concentrations of serum thyroxine (fT4) and triiodothyronine (fT3). The primary choice in hypothyroidism treatment is oral administration of levothyroxine (L-T4), a synthetic T4 hormone, as approximately 100–125 μg/day. Generally, dose adjustment is made by trial and error approach. However, there are several factors which might influence bioavailability of L-T4 treatment. Genetic background could be an important factor in hypothyroid patients as well as age, gender, concurrent medications and patient compliance. The concentration of thyroid hormones in tissue is regulated by both deiodinases enzyme and thyroid hormone transporters. In the present study, it was aimed to evaluate the effects of genetic differences in the proteins and enzymes (DIO1, DIO2, TSHR, THR and UGT) which are efficient in thyroid hormone metabolism and bioavailability of L-T4 in Turkish population. According to our findings, rs225014 and rs225015 variants in DIO2, which catalyses the conversion of thyroxine (pro-hormone) to the active thyroid hormone, were associated with TSH levels. It should be given lower dose to the patients with rs225014 TT and rs225015 GG genotypes in order to provide proper treatment with higher effectivity and lower toxicity.