A study of the role of DIO1 and DIO2 polymorphism in thyroid cancer and drug response to therapy in the Saudi population

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.

Determination of Frequency of Type 2 Deiodinase Thr92Ala Polymorphism (rs225014) in 131I-treated Differentiated Thyroid Cancer Patients Undertaking L-thyroxine (L-T4) Suppression Therapy

“…[ 9 ] No association between DIO2 SNP and thyroid cancer manifestation was observed in this study which is in accordance with previous studies. [ 15 16 28 ] Thyroidectomized DTC patients lack inherent T3 production and hence entirely depend on the DIO1 and DIO2 enzymes for catalytic conversion of L-T4 to T3. DTC patients are given L-T4 therapy to suppress TSH activity to keep the remnant malignant thyroid tissues dormant to inhibit the recurrence of thyroid cancer.…”

“…have speculated that DIO2 SNPs may have an important role in determining the L-T4 dose requirement in thyroidectomized and 131 I-treated DTC patients. [ 15 28 ] Torlontano et al . reported that the homozygous rs225014 variant was associated with approximately 20% higher L-T4 dose requirement to suppress TSH levels in DTC patients.…”

Association between DIO2 Thr92Ala polymorphism and hypertension in patients with hypothyroidism: Korean Genome and Epidemiology Study

“…Several studies have implicated the importance of DIO2 in patients with hypothyroidism; however, the effect of DIO2 polymorphism on BP in patients with hypothyroidism has not been identified. One study focused on the association between DIO1 and DIO2 variants in patients with thyroid cancer undergoing thyroidectomy and treatment with thyroxin [43]. They reported that participants with DIO2 polymorphism, rs1388378_G>T, required a higher hormonal dose; however, they did not suggest the influence of DIO2 polymorphism on disease status or other clinical parameters.…”

Network medicine approaches for identification of novel prognostic systems biomarkers and drug candidates for papillary thyroid carcinoma

“…When we evaluate the compromising 21 nodes of this PTC‐module, we find that several of these genes have already been individually associated with thyroid cancer, which further strengthens our confidence in our observations when we consider them as systems biomarkers. The following genes: PROS1, 42 DCSTAMP, 43 DUSP5, 44 AHNAK2, 45 SLC34A2, 46 FN1, 47 C16orf89, 48 FHL1, 49 TPO, 50 DIO1 51 has been associated with thyroid cancer and/or PTC.…”