Deiodinase Type 3 Polymorphism (rs1190716) Affects Therapeutic Response to Levothyroxine

Abstract

Objectives: Levothyroxine (LT4) is a commonly used treatment for hypothyroidism. Deiodinase enzymes control the metabolism and homeostasis of thyroid hormones (THs). Deiodinase type 3 gene (DIO3) encodes deiodinase type 3 enzyme (D3), and the genetic polymorphisms of this gene could affect the levels of THs and the response to LT4 treatment. This study aimed 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 aged 40 years were enrolled in this cross-sectional study. All of them were already on the LT4 treatment for at least 4 months. THs [thyroxin (T4), triiodothyronine (T3), reverse triiodothyronine (rT3), and diiodothyronine (T2)] were estimated. An 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 T4, T3, and T2 levels among 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 on the therapeutic response to LT4 in Iraqi female patients with primary hypothyroidism. Regarding DIO3 gene, this is a novel finding; hence, further studies are needed to confirm it.