A study of the role of DIO1 and DIO2 polymorphism in thyroid cancer and drug response to therapy in the Saudi population |
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| Affiliation: | 1. Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Kingdom of Saudi Arabia, P.O. Box 2457, Riyadh 11451, Saudi Arabia;2. Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia |
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| Abstract: | BackgroundDeiodinases comprise a group of selenoproteins that regulate the bioavailability of active thyroid hormones (TH) in a time and tissue specific fashion. They increase the hormonal activity by metabolizing their inactive precursors to active forms or terminate their activity by deactivating active hormones. The role of the deiodinase (DIO) gene polymorphisms in thyroid cancer is not fully understood yet. This study evaluated the potential association of the DIO1 and DIO2 genes with differentiated thyroid cancer and differential thyroxine dose requirement in thyroidectomized patients in a Saudi cohort.MethodsWe selected four variants (one DIO1 and three DIO2) for the association studies using Taqman assays in 507 DTC patients undergoing treatment with thyroxin against 560 disease-free individual, all of Saudi Arab origin.ResultsNone of the studied variants was linked to differentiated thyroid cancer. The rs1388378_G > T was initially linked to thyroxine dose requirement (p = 0.035) when all patients were considered together, but this association was lost when the patients were classified into either near suppressed (0.1 ≤ TSH < 0.5) or suppressed (TSH < 0.1) TSH group.DiscussionAlthough the results suggest only a weak relationship with differentiated thyroid cancer, they strongly indicate that the DIO2 polymorphism influences the hormonal dose requirement in patients undergoing treatment with thyroxine. This probably points to a distinction in the way this gene influences disease as compared to therapy thereof. |
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| Keywords: | Differentiated thyroid cancer rs1388378 Deiodinase 1 Deiodinase 2 thyroxine therapy deiodinase (1,2,3) gene D (1, 2)" },{" #name" :" keyword" ," $" :{" id" :" k0040" }," $$" :[{" #name" :" text" ," _" :" deiodinase (1,2) protein FT4" },{" #name" :" keyword" ," $" :{" id" :" k0050" }," $$" :[{" #name" :" text" ," _" :" free thyroxin TH" },{" #name" :" keyword" ," $" :{" id" :" k0060" }," $$" :[{" #name" :" text" ," _" :" thyroid hormone TSHβ" },{" #name" :" keyword" ," $" :{" id" :" k0070" }," $$" :[{" #name" :" text" ," _" :" thyroid-stimulating homorne-β T3" },{" #name" :" keyword" ," $" :{" id" :" k0080" }," $$" :[{" #name" :" text" ," _" :" triiodothyronine T4" },{" #name" :" keyword" ," $" :{" id" :" k0090" }," $$" :[{" #name" :" text" ," _" :" tetraiodothyronine UGT1A" },{" #name" :" keyword" ," $" :{" id" :" k0100" }," $$" :[{" #name" :" text" ," _" :" UDP glucuronosyltransferase family 1 member A WSB-1" },{" #name" :" keyword" ," $" :{" id" :" k0110" }," $$" :[{" #name" :" text" ," _" :" WB repeat and SOCs box-containing UDP" },{" #name" :" keyword" ," $" :{" id" :" k0120" }," $$" :[{" #name" :" text" ," _" :" uridine phosphorylase |
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