Determination of frequency of Type 2 deiodinase Thr92Ala polymorphism (rs225014) in 131I-treated differentiated thyroid cancer patients undertaking L-Thyroxine (L-T4) suppression therapy.

Abstract

Abstract Purpose: Type 2 deiodinase (DIO2) enzyme plays vital role in peripheral T4 to T3 conversion and regulation of TSH secretion. rs225014 is a common single nucleotide polymorphism (SNP) which is known to reduce DIO2 activity. The differentiated thyroid cancer patients (DTC) are given L-T4 therapy after total thyroidectomy and 131I-treatment to suppress TSH levels. This study was undertaken to determine the frequency of rs225014 in DTC patients and its effect on the thyroid function parameters and L-T4 dose. Methods: The study included DTC patients undertaking L-T4 and a control group. Thyroid function tests were estimated by RIA/IRMA and rs225014 SNP was detected by PCR. Results: The frequency of Thr/Thr (wildtype), Thr/Ala (heterozygous mutant) and Ala/Ala (homozygous mutant) genotypes in the DTC patients was 0.21, 0.52 and 0.27 respectively. There was no association between rs225014 and DTC. T3 levels and T3/T4 ratio were significantly low in the DTC patients harbouring Ala/Ala genotype which indicated impaired DIO2 catalysed T4 to T3 conversion. L-T4 dose required to suppress TSH in the DTC patients with Ala/Ala genotype was marginally higher when compared with wild type genotype. Conclusion: The results indicated that DTC patients carrying rs225014 SNP may require higher L-T4 dose to suppress TSH levels due to impaired T4 to T3 conversion in the absence of any other compensatory mechanisms. The screening for rs225014 in the DTC patients showing reduced response to TSH suppression would enable quicker decision-making in the implementation of personalized L-T4 dose and save the patients from development of any adverse effects.