THRA RS939348 POLYMORPHISM AND L-THYROXINE RESPONSE IN IRAQI HYPOTHYROID FEMALES

Abstract

Hypothyroidism is a prevalent endocrine disorder, particularly affecting women and older adults, with potentially serious health impacts if left untreated. Levothyroxine is the standard therapy for primary hypothyroidism; however, its efficacy may be influenced by genetic polymorphisms. This study investigates the influence of the THRA rs939348 T>C polymorphism on L-thyroxine treatment response in Iraqi females with primary hypothyroidism. A cross-sectional study was conducted from September 2023 to July 2024, including 100 hypothyroid female patients on levothyroxine therapy (≥4 months) and 50 healthy female controls. Clinical data and treatment outcomes were gathered through questionnaires and medical records. DNA genotyping for THRA rs939348 was performed using Restriction Fragment Length Polymorphism-PCR (RFLP-PCR), and biochemical analyses assessed thyroid function, glucose, insulin, and lipid profiles. Patients were grouped by THRA rs939348 genotype (TT, TC, CC) and categorized as responders or non-responders based on achieving normalized TSH levels (0.5-5µU/ml). Key findings indicated that among responders, 33% had the TT genotype, while 20% had TC/CC genotypes. Conversely, among non-responders, only 11% had the TT genotype, and 36% had TC/CC genotypes, showing a significant association between the mutant allele and poorer treatment response (P<0.0001). Responders with the TT genotype demonstrated stable TSH levels similar to healthy controls, whereas non-responders with the TC/CC genotypes had TSH levels six times higher than responders and healthy individuals. These results underscore the clinical relevance of THRA rs939348 polymorphism testing, as it may help identify patients at risk for suboptimal treatment response, potentially guiding personalized hypothyroidism management strategies.