تأثيراالاشكال الجينية لجين مستقبلات الغدة الدرقية الفا 1على الاستجابة العلاجية لعقار الليفوثايروكسين عند مريضات قصور الغدة الدرقية في محافظة كربلاء

The Impact of THRA1 gene Polymorphisms on the Therapeutic Response of Levothyroxine in Female Patients with Hypothyroidism in Kerbala Province

Abstract
Background: Thyroid dysfunctions are among the most prevalent
endocrine disorders worldwide, with hypothyroidism being a common
manifestation. clinical hypothyroidism is characterized by elevated
thyroid-stimulating hormone (TSH) levels while free thyroxine (T4)
remains below the normal range. Thyroid hormone receptor alpha 1
(TRα1) plays a crucial role in thyroid function, and genetic variations may
influence treatment responses.
Aim: This study investigates the impact of rs939348 (T>C) and
rs12939700 (C>A) single nucleotide polymorphisms (SNPs) in the TRα1
gene on the therapeutic response to levothyroxine (L-T4) in Iraqi female
patients with hypothyroidism in Kerbala province.
Methodology: A case-control study was conducted on 100 Iraqi female
patients (≥40 years) with primary hypothyroidism undergoing L-T4
therapy, compared with 50 healthy females as controls. Thyroid hormone
levels (free and total T4, free and total T3, TSH) were assessed. The
rs939348 SNP was analyzed using restriction fragment length
polymorphism polymerase chain reaction (RFLP-PCR), while rs12393700
SNP detection was performed using allele specific polymerase chain
reaction (AS-PCR).
Results: The results of this study reveal that rs939348 (T>C) SNP,
genotype distribution in patients was TT: 33%, CC: 48%, and CT: 19%,
compared to TT: 80% and CC, CT: 10% in controls. A significant
XIX
association was found between rs939348 and TSH levels (p < 0.01) as well
as total T3 and free T4 (p < 0.001) compared to controls.
For the rs12393700 (C>A) SNP, genotype distribution in patients was CC:
90%, AA: 4%, and CA: 6%, while all controls exhibited the CC genotype
(100%). A highly significant association (p < 0.001) was observed between
rs12939700 and TSH and free T4 levels.
Conclusion: The rs939348 (T>C) SNP, especially the CT and CC
genotypes, was significantly associated with changes in thyroid hormone
levels, which could contribute to resistance to levothyroxine (L-T4)
therapy. Similarly, the rs12393700 (C>A) SNP showed a strong correlation
with variations in thyroid hormone levels, indicating its potential role in
influencing treatment outcomes. These findings suggest that genetic
variations in the TRα1 gene may affect the efficacy of levothyroxine,
underscoring the importance of adopting personalized treatment
approaches for managing hypothyroidism.