The Contribution of Polymorphisms in TSHR and THRα genes in Clinical Management of Hypothyroid Patients Treated with Levothyroxine

Abstract

Objective : This study was aimed to investigate the clinical and biochemical response to levothyroxine (L-T4) doses in hypothyroid patients in correlation with genetic variation in thyroid stimulating hormone receptor ( TSHR ) gene and thyroid hormone receptor ( THR α) gene. Design : This cross-sectional correlation study includes 228 patients with primary hypothyroidism who were using L-T4 replacement therapy. Thyroid function test was performed using standard techniques. Genotyping of rs939348 at THRα gene, and rs2268458 and rs2239610 at TSHR gene was performed using the polymerase chain reaction-based restriction fragment length polymorphism assay (PCR-RFLP). Patient history of illness, medication and compliance data was collected using patients’ medical files. Results: The THRα rs939348 polymorphism was associated with L-T4 replacement doses in hypothyroid patient and central obesity. No significant correlation between the examined SNPs on TSHR and L-T4 doses or the different clinical and biochemical parameters. Finally, L-T4 dose was associated with lower BMI, waist circumference, and TSH, and higher free T4 (fT4) among hypothyroid patients. Conclusions: Whereas the two tested TSHR polymorphisms were not associated with the dose of T4, the THRα rs939348 polymorphism was associated with L-T4 dose and central obesity among hypothyroid patients. T4 dose is also associated with multiple beneficial effects among hypothyroid patients.