BackgroundThere is a clinical observation in the local population of hypothyroid patients that many patients still have symptoms and disease-complaints even after they treated with levothyroxine as a replacement therapy. Deiodinase type II enzyme play a central role in the conversion of thyroxin to the active form triiodothyronine. This study searches the effect of rs225014; 274 T>C single nucleotide polymorphism (SNP) of deiodinase type II (DIO2) gene on the clinical response to levothyroxine replacement therapy in Iraqi hypothyroidism patients. MethodologyIn this cross –sectional study, one hundred fifty Iraqi female patients with primary hypothyroidism of the age of 40 and above, who were treated with levothyroxine were recruited. Thyroid hormones were assessed and the genetic analysis to detect rs225014 SNP was done using the tetra primers amplification refractory mutation system-polymerase chain reaction technique. ResultsThe genotypes distribution of rs225014; 274 T>C SNP was 22(14.66 %), 19 (12.66 %) and 72(72.66 %) as TT, TC and CC, respectively. Total T4 was significantly higher in TC carriers than in CC carriers, while there were no significant differences in the levels of TSH, total T3, free T3 and free T4 in TT, TC and CC groups of patients. The TC group also had significantly higher fasting serum insulin and homeostatic model assessment for insulin resistance (HOMA-IR) than the carriers of CC genotype. ConclusionsSince the rs225014 SNP of DIO2 gene is not associated with the most of the thyroid hormones levels, it could not affect the response to levothyroxine treatment in our sample of Iraqi hypothyroidism patients. Although this SNP cannot be excluded from being related to the hypothyroidism because the homozygous mutant type (CC) of it is the most frequent genotype in our sample of Iraqi hypothyroidism patients. Since TC genotype is associated with elevated levels of fasting serum insulin and HOMA-IR, it could have an impact in developing insulin resistance and type 2 diabetes mellitus.