Deiodinase Type III Polymorphism (Rs1190716) Affects The Therapeutic Response to Levothyroxine Short Title: Deiodinase Type III Gene and Hypothyroidism

Objectives : Levothyroxine (LT4) is the commonly used treatment for hypothyroidism. Deiodinases enzymes control the metabolism and homeostasis of thyroid hormones (THs). Deiodinases type III (DIO3) gene encodes deiodinase type 3 enzyme (D3), the genetic polymorphisms of this gene could affect the levels of THs and then the response to LT4 treatment. This study aims to investigate the single nucleotide polymorphism (SNP), rs1190716; C>T, of DIO3 as a candidate genetic variant that might affect the clinical response to LT4 treatment. Materials and Methods: Two hundred Iraqi hypothyroid female patients who were aged 40 years or older were enrolled in this cross-sectional study. All of them were already on the LT4 treatment for at least 4 months. Thyroid hormones (thyroxin (T4), triiodothyrionine (T3), revers riiodothyrionine (rT3) and diiodothyrionine (T2)) were estimated. Allele specific-polymerase chain reaction technique was performed to detect the rs1190716; C>T SNP. Results: The genotypes distribution of rs1190716; C>T SNP was 10 (4.5%) for the wild type (CC), 50 (22.7%) for the heterozygous mutant type (TC), and 160 (72.7%) for the homozygous mutant type (TT). The patients were divided into three groups according to their genotypes. Significant differences were found in the levels of T4, T3 and T2 among the groups of the patients (P=0.019, P=0.039, P= 0.032, respectively) Conclusion: The rs1190716; C>T SNP could affect the activity of the D3 enzyme and the metabolic homeostasis of the THs, therefore rs1190716; C>T SNP could have an impact in the therapeutic response to LT4 in Iraqi female patients with primary hypothyroidism. Regarding the DIO3 gene, this is a novel finding, hence further studies are needed to conform it.