Study of DIO2 Thr92Ala Genetic Polymorphism (rs225014) in Hypothyroid Patients Who Achieved Biochemical Euthyroidism

Abstract

Background: Many hypothyroid patients often experience persistent symptoms despite being biochemically euthyroid on levothyroxine replacement. type 2 deiodinase activates triiodothyronine from thyroxine. DIO2 Thr92Ala genetic polymorphisms are associated with a variety of clinical conditions. This study aimed to assess the relationship between DIO2 Thr92Ala (rs225014) polymorphism and persistent hypothyroid symptoms in levothyroxine treated hypothyroid patients and achieved biochemical euthyroidism. Methods: This case-control study was carried out on 144 participants attending outpatient endocrinology clinics at Menoufia university hospitals from November 2022 to June 2024. Participants were categorized into three groups of 48 each: Group A: matched for age and sex with a normal thyroid profile. Group B: symptomatic hypothyroid patients on levothyroxine, achieving biochemical euthyroidism for 6 months. Group C: Asymptomatic hypothyroid patients on levothyroxine, also achieving biochemical euthyroidism for 6 months. History-taking, clinical examination, and investigations, which included the genotyping of DIO2 Thr92Ala (rs225014) using Real-time PCR, were administered to all participants. Results: There was no association among the DIO2 Thr92Ala genetic variation (rs225014) and the following: anti-thyroid peroxidase antibody titer, free triiodothyronine, thyroid stimulating hormone, free thyroxine, illness duration, or levothyroxine dosage. In group B, it correlated significantly with certain thyroid-related quality of life (THYPRO39) questionnaire subscales like tiredness, daily life and overall score. In group C, only the emotional subscale was associated (p-value <0.05). Conclusion: DIO2 polymorphism rs225014 may be correlated with chronic hypothyroid symptoms but not correlated with TSH level or levothyroxine dosage. Keywords: Deiodinase type 2, genetic polymorphisms, Hypothyroidism, levothyroxine, ThyPRO39 questionnaire.