Genetic Polymorphisms of Thyroid Stimulating Hormone Receptor, Iodothyronine Deiodinase-1 and Phosphodiesterase 8 Beta among Women with Thyroid Disorders in White Nile State

Abstract

A case control study conducted during the period from June 2013 to Septemper 2016 to assess the genetic polymorphisms of thyroid related genes, they were Iodo thyronine deiodinase-1 (DIO1) (a & b), Phosphodiesterase 8B (PDE8B) and Thyroid Stimulating Hormone Receptor (TSHR) and its relationship to pathogenesis of thyroid disorders in White Nile State in Sudan. One hundred Sudanese women diagnosed with thyroid disorders classified as (30 hypothyroidism, 30 hyperthyroidism and 40 euthyroid goiter) enrolled in this study as a test group whose admitted to the health insurance hospital in White Nile State, age range 22.1-47.5years old and fifty apparently healthy matched individuals age range 22.8-49.4 years old as control group, Blood specimens were collected and the levels of free thyroxin (FT4), free triiothyroinine (FT3) and thyroid stimulating hormone (TSH) in serum were measured by microplate immuno enzymatic assay with commercial kits from Omega Company. From blood sample DNA was extracted using phenol chloroform method and polymerase chain reaction was performed and the PCR products were used for restriction fragment length polymorphism to identify the specific alleles of genes. DNA purification and standard sequencing was performed and analyzed by bioinformatics analysis to confirm the results of RFLP analysis. The Data were computed and analyzed using statistical package for social sciences (SPSS Version 20) computer soft ware. The results of the study showed that, there was significantly decrease of the mean of TSH levels p-value (0.020) euthyroid goiter when compared with control group. Also the study indicated that, there was a significant association between DIO1a gene polymorphism and euthyroid goiter p-value (0.002). A Novel mutation was detected in five patients with thyroid disorders (3 patients with hypothyroidism, one with hyperthyroidism and one with euthyroid goiter) when standard DNA sequencing was performed. The results also showed a significant association between DIO1b gene polymorphism and hypothyroidism p-value (0.001). On the other hand PDE8B gene polymorphism significantly associated with hyperthyroidism, hypothyroidism and euthyroid goiter (p-value = 0.009, 0.010, 0.008), also TSHR gene polymorphism was significantly associated with the three types of thyroid disorders (hyperthyroidism p-value (0.009), hypothyroidism p-value (0.004) and euthyroid goiter p-value (0.016). Significant decreased of FT4 levels was observed when compared mutant allele (DIO1a) with normal allele in hyperthyroidism p- value (0.040) and euthyroid goiter p-value (0.020) while FT3 and TSH levels were unchanged. In addition there was significant increased of FT3 p-value (0.001) and FT4 levels p-value (0.001) and significant decreased of TSH level p-value (0.010) when compare mutant allele (PDE8B) with normal in hyperthyroidism. Finally these genes may contribute to pathogenesis of related disorders. In addition TSHR and PDE8B genes polymorphisms link with hyperthyroidism, hypothyroidism and euthyroid goiter therefore could be a useful prognostic marker for thyroid disorders.