The Role of Type II Deiodinase Polymorphisms in Clinical Management of Hypothyroid Patients Treated with Levothyroxine

Study Objective: Several factors can affect achieving the goals with levothyroxine (L-T4) therapy. This study investigates the clinical and biochemical response to L-T4 replacement therapy in hypothyroid patients in correlation with genetic variation in Deiodinase type II (DIO2) gene. Design and setting: This is a cross-sectional correlation study. The setting was the diabetes and endocrinology clinics at 2 Jordanian Hospitals. Methodology: Patients with primary hypothyroidism who are controlled on stable L-T4 replacement therapy were recruited and thyroid function test was performed. Genetic analysis to detect 4 single nucleotide polymorphisms (SNPs) rs225011, rs7140952, rs225012 and rs2839858 in DIO2 gene was carried out using the polymerase chain reaction-based restriction fragment length polymorphism assay (PCR-RFLP). Results: There was no correlation between the 4 SNPs in DIO2 gene and replacement doses of L-T4, whereas a statistical significance was found between rs7140952 and central obesity (P<0.05), and systolic and diastolic blood pressure (P<0.05). The dose of L-T4 was associated with lower levels of TSH, fT4, central obesity, body mass index and waist circumference. Conclusion: While L-T4 dose is associated with several positive effects on hypothyroid patients, none of the examined SNPs in DIO2 is correlated with replacement doses of the drug. However, rs7140952 polymorphism is associated with components of metabolic syndrome including blood pressure and central obesity.