تأثيرتعددالاشكال الجينيه لجين الديايودينيز- النوع الثالث على الأستجابة العلاجية لعقار الليفوثايروكسين عند مريضات قصور الغدة الدرقية في محافظة كربلاء

The Impact of Deiodinase-3 gene Polymorphisms on the Therapeutic Response of Levothyroxine in Hypothyroidism Female Patients in Kerbala Province

Abstract
Background: Different factors influence obtaining the target of treatment with levothyroxine (L-T4) replacement therapy, therefore, many patients remain have persistent symptoms of hypothyroidism even when they are taking this treatment. Deiodinase type-3 enzyme converts thyroxine (T4) to reverse triiodothyronine (rT3) and triiodothyronine (T3) to diiodothyronine (T2). Consequently it plays important role in regulating thyroid hormones homeostasis.
Aim: This study investigates the effects of rs945006; T>G and rs1190716; C>T single nucleotide polymorphisms (SNPs) in the deiodinase type-3 gene on the therapeutic response to L-T4 in a sample of Iraqi hypothyroidism female patients living in Kerbalaa province.
Methodology: Two hundred twenty hypothyroid female patients aged 40 years or older who were on L-T4 treatment for at least 4 months were enrolled in this cross-sectional study. Thyroid hormones (T4, T3, rT3 and T2) and thyroid stimulating hormone were assessed. The genetic analysis to detect rs945006; T>G SNP and rs1190716; C>T SNP was done using the tetra primers amplification refractory mutation system- polymerase chain reaction technique.
Results: Genotypes distribution of rs945006; T>G SNP was 25 (11.4%) for the wild type (TT), 50 (22.7%) for the heterozygous mutant type (TG), and 145 (65.9%) for the homozygous mutant type (GG). The patients were divided into three groups according to their genotypes. Non significant differences was found in the serum thyroid hormones levels among the groups of the three genotypes carriers. The genotypes distribution of rs1190716; C>T SNP was 10 (4.5%) for the wild type (CC), 50 (22.7%) for the heterozygous mutant type (TC), and 160 (72.7%) for the homozygous mutant type (TT). Significant differences (P ≤ 0.05) were found in the levels of T4, T3 and T2 among the groups of the patients (P=0.019, P=0.039, P= 0.032, respectively)
Conclusion: Since the rs945006 SNP is not associated with the serum thyroid hormones levels, it might not affect the response to L-T4 treatment. The rs1190716; C>T SNP could affect the activity of the deiodinase type-3 enzyme and the metabolic homeostasis of the thyroid hormones, therefore rs1190716; C>T SNP could have an impact in the therapeutic response to L-T4 in Iraqi female patients with primary hypothyroidism. This is a novel finding, hence further studies are needed to confirm it.