Association of DIO1 rs2235544 Polymorphism with Thyroid Hormone Profile and Levothyroxine Dose Requirement in Iraqi Women with Primary Hypothyroidism

Sara Zuhair Ghani; Haider F. S. Al-Zubaidy

doi:10.24017/science.2026.2.7

Authors

Sara Zuhair Ghani Department of Clinical Laboratory Sciences, College of Pharmacy, University of Kufa, Najaf, Iraq | Najaf Health Directorate, Najaf, Iraq. Author https://orcid.org/0009-0001-2611-0895
Haider F. S. Al-Zubaidy Department of Clinical Laboratory Sciences, College of Pharmacy, University of Kufa, Najaf, Iraq. Author

DOI:

https://doi.org/10.24017/science.2026.2.7

Keywords:

DIO1, Rs2235544, Hypothyroidism, evothyroxine, pharmacogenetics, Thyroid hormones, Deiodinase

Abstract

Type 1 iodothyronine deiodinase (DIO1) plays an important role in peripheral thyroid hormone metabolism, and genetic variation in DIO1 may be associated with differences in thyroid hormone profiles and levothyroxine (LT4) dosing. The present study investigated the association of DIO1 rs2235544 polymorphism with thyroid hormone parameters and the current prescribed LT4 dose in Iraqi women with primary hypothyroidism. A cross-sectional study was conducted among 76 women receiving LT4 monotherapy. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels were tested, and the FT3/FT4 ratio was calculated. DIO1 rs2235544 polymorphism was genotyped using real-time PCR-based probe allelic discrimination. Demographic, biochemical and treatment-related variables were compared across the genotype groups. Multiple linear regression analysis was used to evaluate the factors associated with the current prescribed LT4 dose. There were significant differences in body mass index (BMI) and LT4 dose between the genotype groups (both P < 0.001). The mean BMI was 28.43, 26.89, and 25.81 kg/m² in the homozygous (AA), heterozygous (CA) and homozygous (CC) genotypes, respectively, while the mean LT4 dose was 126.79, 124.07, and 79.76 µg/day, respectively. No significant differences were observed in TSH (P = 0.552), FT3 (P = 0.462), FT4 (P = 0.975), or the FT3/FT4 ratio (P = 0.785). These findings suggest an association between DIO1 rs2235544 and the current prescribed LT4 dose in Iraqi women with primary hypothyroidism. Further studies are required to confirm this association.

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