Thyroglobulin Gene Research Articles

Rare and common genetic variations in the Keap1/Nrf2 antioxidant response pathway impact thyroglobulin gene expression and circulating levels, respectively

Nuclear factor, erythroid 2-like 2 (Nrf2) is a transcription factor that has been gaining attention in the field of pharmacology and especially in the chemoprevention of diseases such as cancer, metabolic and neurodegenerative diseases, etc. This is because natural compounds such as sulforaphane, which is found in broccoli sprout extracts, can activate Nrf2. The repertoire of the roles of Nrf2 is ever increasing; besides its traditional antioxidant and cytoprotective effects, Nrf2 can have other functions as a transcription factor. We have recently shown that Nrf2 directly regulates the expression of thyroglobulin (Tg), which is the most abundant thyroidal protein and the precursor of thyroid hormones. Two functional binding sites for Nrf2 (antioxidant response elements, AREs) were identified in the regulatory region of the TG gene. Interestingly, we then observed that one of these AREs harbors a rare single-nucleotide polymorphism (SNP). Also recently, we performed the first genome-wide association study (GWAS) for common SNPs that impact the circulating levels of Tg. Based on these investigations, we were triggered (i) to investigate whether common SNPs in the Nrf2 pathway correlate with circulating Tg levels; and (ii) to examine whether the rare SNP in one of the TG regulatory AREs may affect gene expression. To address the first question, we analyzed GWAS data from a general population and its two subpopulations, one with thyroid disease and/or abnormal thyroid function tests and the other without, in which circulating Tg levels had been measured. Statistically significant associations with Tg levels were observed in the genes encoding Nrf2 and Keap1, including, notably, a known functional SNP in the promoter of the gene encoding Nrf2. Regarding the rare SNP (rs778940395) in the proximal ARE of the TG enhancer, luciferase reporter gene expression studies in PCCL3 rat thyroid follicular cells showed that this SNP abrogated the basal and sulforaphane- or TSH-induced luciferase activity, behaving as a complete loss-of-function mutation. Thus, both rare and common genetic variation in the Keap1/Nrf2 pathway can impact TG expression and Tg circulating levels, respectively.

Genetic Characterization of Thyroglobulin and Leptin Genes in Pasundan Cattle at West Java

The Thyroglobulin (TG) and Leptin (LEP) genes are two candidate genes that widely used for molecular selection to improve carcass traits in beef cattle. This research was carried out to identify the genetic characterization of TG and LEP genes from 47 heads of Pasundan cows at West Java using PCR-RFLP method. Research shows that TG gene of Pasundan cattle is monomorphic with C allele as the dominant allele (1.00). However, LEP gene of Pasundan cattle is polymorphic with C allele as the dominant allele (0.98) and T as the rare allele (0.02). The polymorphic informative content (PIC) and numberof effective allele (ne) values in the LEP gene in the animal studied were 0.04 and 1.04 respectively. It was concluded that TG/BstYI and LEP/Sau3AI gene in the present study can not be used as molecular selection in Pasundan cattle. These results are important as the basic information for preparing the molecular selection program in the future.

Endocrine systems of the skin.

Apart from its protective function, the skin is also both hormonally and metabolically active. Many hormones are produced in the skin and the regulation of these changes is controlled, as are other organs, by the pituitary gland and hypothalamus. Under the influence of stress factors such as ultraviolet radiation, many reactions are stimulated. After exposure to light in keratinocytes apart from eumelanin, also proopiomelanocortin, dopamine, and opioid substances – β-endorphins are produced. The skin also has a hypothalamic-pituitary-adrenal axis homolog. A corticotropin-releasing hormone is produced and reacts with its skin receptors that lead to, among others, increasing vascular permeability or induce keratinocytes differentiation. A similar homologous system found in skin structures is the hypothalamic-pituitary-thyroid axis, which is expressed by the presence of e.g. thyroid-stimulating hormone (TSH) receptors or thyroglobulin genes. Our review presents selected hormonal skin systems, reactions within them and their products.

Determining Specific Thyroid Transcripts in Peripheral Blood: A Single Center Study Experience.

Thyroid carcinoma (TC) comprises a spectrum of different tumors with a wide range of biological behavior and prognosis. The techniques based on the latest trends in molecular biology may have application in diagnosis of metastatic TC. The aim of this study was to apply and analyze mRNA expression in peripheral blood of thyrotropin receptor [thyroid stimulating hormone receptor (TSHR-mRNA)] gene and thyroglobulin (Tg-mRNA) gene using 2–ΔΔCt method in differentiated TC patients and healthy individuals. Fifty-seven subjects were included in the study, consisting of 40 patients with TC and 17 healthy volunteers as a control group. Total RNA was isolated from peripheral blood and used for two-step reverse transcriptase-polymerase chain reaction (PCR). Real-time PCR was performed with appropriate primers. Relative quantification using the 2–ΔΔCt method was applied. Thyroid carcinoma patients with metastatic disease or loco-regional relapse expressed TSHR-mRNA by a 8.57-fold higher level than healthy controls. Thyroid carcinoma patients with biochemical relapse expressed TSHR-mRNA by a 14.17-fold higher level than healthy controls, while expression of Tg-mRNA was 6.6-fold higher in TC patients with metastatic disease and loco-regional relapse than healthy controls and 8.34-fold higher level compared with TC patients with excellent response to treatment. Our preliminary study showed that the TSHR gene expression might have more useful application as a biomarker compared to detection of Tg gene expression.

Relationship of the bovine IGF1, TG, DGAT1 and MYF5 genes to meat colour, tenderness and cooking loss

Bovine insulin-like growth factor 1 (IGF1), thyroglobulin (TG), diacylglycerol-O-acyltransferase 1 (DGAT1) and myogenic factor 5 (MYF5) genes play an important role in the physiology of lipid and muscle metabolism and are therefore considered as candidate genes for meat production traits in farm animals. The objectives of this study were to investigate single nucleotide polymorphisms (SNPs) in IGF1, TG, DGAT1 and MYF5 genes and to evaluate whether these polymorphisms affected meat colour, tenderness and cooking loss in Holstein cattle. Initially, the SNPs were detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method. Meat samples (N= 50) derived from M. longissimus thoracis et lumborum (LTL) were used in the current study. Significant differences in variations of meat colour parameters were observed at 24 hours post-mortem. IGF1 was associated with colour parameters of a* and chroma values. In addition, effects of TG were statistically significant on L* and a* values, while, effects of MYF5 were significant on a* value. There was no association of the tested SNPs with meat pH, tenderness and cooking loss. The results presented here may give the valuable information for improving meat colour in cattle.

Unraveling molecular targets of bisphenol A and S in the thyroid gland.

Bisphenol A (BPA) is a well-known endocrine disruptor with several effects on reproduction, development, and cancer incidence, and it is highly used in the plastic industry. Bisphenol S (BPS) was proposed as an alternative to BPA since it has a similar structure and can be used to manufacture the same products. Some reports show that BPA interferes with thyroid function, but little is known about the involvement of BPS in thyroid function or how these molecules could possibly modulate at the same time the principal genes involved in thyroid physiology. Thus, the aims of this work were to evaluate in silico the possible interactions of BPA and BPS with the thyroid transcription factors Pax 8 and TTF1 and to study the actions in vivo of these compounds in zebrafish thyroid gene expression. Adult zebrafish treated with BPA or BPS showed that sodium iodide symporter, thyroglobulin, and thyroperoxidase genes were negatively or positively regulated, depending on the dose of the exposure. Human Pax 8 alignment with zebrafish Pax 8 and Rattus norvegicus TTF1 alignment with zebrafish TTF1 displayed highly conserved regions in the DNA binding sites. Molecular docking revealed the in silico interactions between the protein targets Pax 8 and TTF1 with BPA and BPS. Importance of some amino acids residues is highlighted and ratified by literature. There were no differences between the mean energy values for BPA docking in Pax 8 or TTF1. However, BPS energy values were lower in TTF1 docking compared to Pax 8 values. The number of amino acids on the protein interface was important for Pax 8 but not for TTF1. The main BPA interactions with proteins occurred through Van der Waals forces and pi-alkyl and alkyl interactions, while BPS interactions mainly occurred through carbon hydrogen bonds and conventional hydrogen bonds in addition to Van der Waals forces and pi-alkyl interactions. These data point to a possible interaction of BPA and BPS with Pax 8 and TTF1.

Analysis of IGF1 C472T and TG C422T polymorphisms in Turkish Grey Steppe and Holstein Crossbred Bulls (Boz Irkı ve Holstein Melezi Erkek Sığırlarda IGF1 C472T ve TG C422T Polimorfizmlerinin Analizi)

The aim of the study was to determine genotypic distribution of bovine insulin-like growth factor 1 and thyroglobulin genes in Turkish Grey Steppe (Boz) and Holstein crossbred bulls. In the study, unrelated 30 Turkish Grey and 26 Holstein crossbred cattle were used. Genomic DNA was isolated from whole blood using standart phenol-chloroform extraction method. The polymerase chain reaction-restriction fragment length polymorphism technique was used for genotyping of C472T and C422T polymorphisms in insulin-like growth factor 1 and thyroglobulin genes, respectively. Hardy-Weinberg equilibrium was calculated by using PopGene software program. In addition the population indexes including heterozygosity, number of effective alleles and polymorphism information content were determined on the basis of allelic distribution. For insulin-like growth factor 1 gene, A allele frequency was higher and BB genotype was not present in both breed groups. For thyroglobulin gene, TT genotype was not present and moreover C allele was almost fixed in both Turkish Grey and Holstein crossbred bulls. In addition, extremely low minor allele frequencies in resulted in low genetic variabilities of population indexes. The present results may be useful for future studies conducted on bovine genome with respect to insulin-like growth factor 1 and thyroglobulin genes.

A novel mutation in the TG gene (G2322S) causing congenital hypothyroidism in a Sudanese family: a case report

BackgroundCongenital hypothyroidism (CH) has an incidence of approximately 1:3000, but only 15% have mutations in the thyroid hormone synthesis pathways. Genetic analysis allows for the precise diagnosis.Case presentationA 3-week old girl presented with a large goiter, serum TSH > 100 mIU/L (reference range: 0.7–5.9 mIU/L); free T4 < 3.2 pmol/L (reference range: 8.7–16 pmol/L); thyroglobulin (TG) 101 μg/L. Thyroid Tc-99 m scan showed increased radiotracer uptake. One brother had CH and both affected siblings have been clinically and biochemically euthyroid on levothyroxine replacement. Another sibling had normal thyroid function. Both Sudanese parents reported non-consanguinity. Peripheral blood DNA from the proposita was subjected to whole exome sequencing (WES). WES identified a novel homozygous missense mutation of the TG gene: c.7021G > A, p.Gly2322Ser, which was subsequently confirmed by Sanger sequencing and present in one allele of both parents. DNA samples from 354 alleles in four Sudanese ethnic groups (Nilotes, Darfurians, Nuba, and Halfawien) failed to demonstrate the presence of the mutant allele. Haplotyping showed a 1.71 centiMorgans stretch of homozygosity in the TG locus suggesting that this mutation occurred identical by descent and the possibility of common ancestry of the parents. The mutation is located in the cholinesterase-like (ChEL) domain of TG.ConclusionsA novel rare missense mutation in the TG gene was identified. The ChEL domain is critical for protein folding and patients with CH due to misfolded TG may present without low serum TG despite the TG gene mutations.

CHARACTERISTICS OF UKRAINIAN GREY CATTLE BY DNA-MARKERS

CHARACTERISTICS OF UKRAINIAN GREY CATTLE BY DNA-MARKERS

Molecular analysis of thyroglobulin mutations found in patients with goiter and hypothyroidism.

Thyroid dyshormonogenesis due to thyroglobulin (TG) gene mutations have an estimated incidence of approximately 1 in 100,000 newborns. The clinical spectrum ranges from euthyroid to mild or severe hypothyroidism. Up to now, one hundred seventeen deleterious mutations in the TG gene have been identified and characterized. The purpose of the present study was to identify and characterize new mutations in the TG gene. We report eight patients from seven unrelated families with goiter, hypothyroidism and low levels of serum TG. All patients underwent clinical, biochemical and image evaluation. Sequencing of DNA, genotyping, as well as bioinformatics analysis were performed. Molecular analyses revealed three novel inactivating TG mutations: c.5560G>T [p.E1835*], c.7084G>C [p.A2343P] and c.7093T>C [p.W2346R], and four previously reported mutations: c.378C>A [p.Y107*], c.886C>T [p.R277*], c.1351C>T [p.R432*] and c.7007G>A [p.R2317Q]. Two patients carried homozygous mutations (p.R277*/p.R277*, p.W2346R/p.W2346R), four were compound heterozygous mutations (p.Y107*/p.R277* (two unrelated patients), p.R432*/p.A2343P, p.Y107*/p.R2317Q) and two siblings from another family had a single p.E1835* mutated allele. Additionally, we include the analysis of 48 patients from 31 unrelated families with TG mutations identified in our present and previous studies. Our observation shows that mutations in both TG alleles were found in 27 families (9 as homozygote and 18 as heterozygote compound), whereas in the remaining four families only one mutated allele was detected. The majority of the detected mutations occur in exons 4, 7, 38 and 40. 28 different mutations were identified, 33 of the 96TG alleles encoded the change p.R277*. In conclusion, our results confirm the genetic heterogeneity of TG defects and the pathophysiological importance of the predicted TG misfolding and therefore thyroid hormone formation as a consequence of truncated TG proteins and/or missense mutations located within its ACHE-like domain.

Multiple approaches to assess the effects of F-53B, a Chinese PFOS alternative, on thyroid endocrine disruption at environmentally relevant concentrations

A Chinese perfluorooctane sulfonate (PFOS) substitute frequently detected in the environment, 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), has a similar structure to PFOS and it is proposed to cause thyroid dysfunction. To further confirm this hypothesis, the effects of F-53B on the thyroid endocrine system and underlying mechanisms were investigated in vitro and in vivo using rat pituitary GH3 cells and developing zebrafish, respectively. In GH3 cells, F-53B enhanced cell proliferation in a dose-dependent manner, indicative of thyroid receptor agonistic activity. In zebrafish larvae, F-53B exposure induced significant developmental inhibition and increased thyroxine (T4) but not 3,5,3′-triiodothyronine (T3) levels accompanied by a decrease in thyroglobulin (TG) protein and transcript levels of most genes involved in the hypothalamic-pituitary-thyroid (HPT) axis. Interestingly, T4 levels remained significantly increased while TG protein and gene transcription levels were markedly upregulated after depuration. Molecular docking studies revealed that F-53B binds to transthyretin (TTR) by forming hydrogen bonds with Lys123 and Lys115, thereby interfering with thyroid hormone homeostasis. Our collective in vitro, in vivo and in silico studies provide novel evidence that F-53B disrupts the thyroid endocrine system at environmentally relevant concentrations, which cannot be recovered after depuration. Given the persistence of F-53B in the environment, the long-term consequences of thyroid hormone disruption by this chemical warrant further investigation.

Monogenic Hashimoto thyroiditis associated with a variant in the thyroglobulin (TG) gene

BackgroundRisk of autoimmune thyroid disease (AITD) is strongly heritable. Multiple genes confer increased risk for AITD, but a monogenic origin has not yet been described. We studied a family with apparent autosomal dominant, early onset Hashimoto thyroiditis. MethodsThe family was enrolled in an IRB-approved protocol. Whole exome sequencing was used to study the proband and an affected sibling. The identified variant was studied in other family members by Sanger sequencing. ResultsWe identified a previously unreported splice site variant in the thyroglobulin gene (TG c.1076-1G > C). This variant was confirmed in all affected family members who underwent testing, and also noted in one unaffected child. The variant is associated with exon 9 skipping, resulting in a novel in-frame variant transcript of TG. ConclusionWe discovered a monogenic form of AITD associated with a splice site variant in the thyroglobulin gene. This finding raises questions about the origins of thyroid autoimmunity; possible explanations include increased immunogenicity of the mutated protein or thyroid toxicity with secondary development of anti-thyroid antibodies. Further study into the effects of this variant on thyroid function and thyroid autoimmunity are warranted.

Genetic polymorphism analysis of 5' untranslated region of thyroglobulin gene in Bali cattle (Bos javanicus) from three different regions of Indonesia

The g.422C&gt;T nucleotide variations in the 5’ untranslated region (5’UTR) of TG gene (called as TG5) has been reported to be associated with level in intramuscular fat (IMF) content or marbling in beef cattle. The objective of this study was to confirm genetic polymorphism of TG5 gene in Bali cattle populations from three different regions as the main resources of Bali cattle in Indonesia. A total of 200 head of Bali cattle have been performed genotyping on TG5 gene using polymerase chain reaction-restriction fragment lenght polymorphism (PCR-RFLP) method and sequence analysis. Results of the study confirmed that TG5 was monomorphic in Bali cattle wherever their origin regions. Moreover, nine candidate SNPs were detected within 5’UTR of TG gene in Bali cattle compared to Genbank reference sequences, although no SNP variations among Bali cattle sample studied. The new other genetic markers within an entire TG gene suggested to be explored and verified for their polymorphisms in Bali cattle. The nine candidate SNPs were also required further verification and validation in a larger sample to be regarded as new SNPs between Bali cattle and Genbank reference sequences.

Association of the polymorphisms in the gene encoding thyroglobulin with the development and prognosis of autoimmune thyroid disease

Graves’ disease (GD) and Hashimoto’s disease (HD) are autoimmune thyroid diseases (AITDs), and the prognosis of AITDs is different for each patient. We examined the association of polymorphisms in the Thyroglobulin (TG) gene with the pathogenesis of AITD. We genotyped TG rs180195G/A, rs853326G/A, rs2076740C/T, rs2703013G/T, rs2958692C/T and rs733735A/G polymorphisms in 137 HD patients, 131 GD patients and 89 healthy controls and also examined the levels of TG mRNA expression and serum TG. The TG rs180195 GG genotype was more frequent in HD patients (p = .0277), and the proportion of CD4+ cells with high levels of TG mRNA was greater in individuals with the GG genotype than in A carriers (p = .0107). The TG rs2703013 TT genotype was less frequent in AITD (p = .0186), and serum TG levels were lower in individuals with the TT genotype than in G carriers (p = .0170). In the TG rs2958692 polymorphism, the T allele was more frequent in intractable GD than in GD in remission (p = .0055), and serum titres of anti-thyroglobulin antibody (TgAb) were lower in GD patients with the TT genotype than in C carriers (p = .0151). In the TG rs2076740 polymorphism, serum titres of TgAb were higher in HD patients who were T carriers than in those with the CC genotype (p = .0359). SNPs in the TG gene were associated with the development of HD and GD, the intractability of GD, and the levels of TG mRNA expression, serum TG, and serum TgAb.

Single nucleotide polymorphism 1623 A/G (rs180195) in the promoter of the Thyroglobulin gene is associated with autoimmune thyroid disease but not with thyroid ophthalmopathy.

BackgroundOur studies over recent years have focused on some new ideas concerning the pathogenesis for the orbital reaction that characterizes Graves’ ophthalmopathy namely, that there are antigens expressed by thyroid tissue and orbital tissue where they are targeted by autoantibodies and/or sensitized T cells, leading to orbital inflammation. While this has been well studied for the thyroid stimulating hormone-receptor, the possible role of another major thyroid antigen, Thyroglobulin (TG), has been largely ignored.MethodsWe identified novel variant 1623 A/G single nucleotide polymorphism (SNP) (rs180195) in the promoter of TG gene associated with autoimmune thyroid disorders. We genotyped the TG SNPs rs2069566, rs2076739, rs121912646, rs121912647, rs121912648, rs121912649, rs121912650, rs137854433, rs137854434, and rs180195 by MassARRAY SNP analysis using iPLEX technology in a cohort of 529 patients with thyroid autoimmunity with and without ophthalmopathy, and controls.ResultsWe showed that variant 1623 A/G SNP (rs180195) in the promoter of TG gene is a marker for thyroid autoimmunity, but not for ophthalmopathy. We showed that there was a significant difference in the distribution of the major allele (G) vs minor allele (A) in patients with Hashimoto’s thyroiditis (HT). In HT the wild-type (GG) genotype was less common. We showed that the genotypes homozygous AA and heterozygous GA rs180195 SNP in the promoter of TG gene were more closely associated with thyroid autoimmunity than the wild-type (GG) polymorphism, and are thus, markers of autoimmunity.Conclusionrs180195 SNP was previously identified by Stefan et al independently of us, who showed that this TG SNP predisposed to autoimmune thyroid diseases. However, this is the first study to explore the association between TG SNPs and HT. Our findings support the notion that the thyroid and orbital disorders are not part of the same disease, ie, “Graves’ disease” or “Hashimoto’s disease”, but separate autoimmune disorders.

Bovine thyroglobulin gene polymorphisms and their association with sexual precocity in Guzerat bulls.

Puberty is a stage of sexual development determined by the interaction of environmental factors and genetic mechanisms. Among them, thyroid function plays a key role in sexual development and spermatogenic function and is under the control of several genes, including the well-described thyroglobulin gene (TG). Previous reports have shown genetic association between thyroid function and selected single nucleotide polymorphisms (SNPs) in taurine cattle. Therefore, the identification of genetic mechanisms involved in the regulation of this trait can assist with the selection for early pubertal bulls, thus improving genetic progress in livestock breeding. The aim of this study was to validate the association between TG SNPs and age at puberty in zebuine bulls. Three SNPs (rs110406764, rs109662686, rs109057985) were genotyped in 159 Guzerat animals using SEQUENOM technology. Results showed a significant association (p<.05) between the studied SNPs and puberty age, in agreement with our previous reports in a taurine breed. Interestingly, allele frequencies were different from those already reported, being GAT the most favourable allele for age at puberty in Guzerat (94.4days lower). Overall, our findings corroborate previous reports and reinforce the importance of genetic influence in the regulation of sexual development and puberty through a thyroid pathway in zebuine cattle.

Waterborne exposure to BPS causes thyroid endocrine disruption in zebrafish larvae.

Bisphenol S (BPS) is widely used as a raw material in industry, resulting in its ubiquitous distribution in natural environment, including the aqueous environment. However, the effect of BPS on the thyroid endocrine system is largely unknown. In this study, zebrafish (Danio rerio) embryos were exposed to BPS at 1, 3, 10, and 30 μg/L, from 2 h post-fertilization (hpf) to 168hpf. Bioconcentration of BPS and whole-body thyroid hormones (THs), thyroid-stimulating hormone (TSH) concentrations as well as transcriptional profiling of key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were examined. Chemical analysis indicated that BPS was accumulated in zebrafish larvae. Thyroxine (T4) and triiodothyronine (T3) levels were significantly decreased at ≥ 10 and 30 μg/L of BPS, respectively. However, TSH concentration was significantly induced in the 10 and 30 μg/L BPS-treated groups. After exposure to BPS, the mRNA expression of corticotrophin releasing hormone (crh) and thyroglobulin (tg) genes were up-regulated at ≥10 μg/L of BPS, in a dose-response manner. The transcription of genes involved in thyroid development (pax8) and synthesis (sodium/iodide symporter, slc5a5) were also significantly increased in the 30 μg/L of BPS treatment group. Moreover, exposure to 10 μg/L or higher concentration of BPS significantly up-regulated genes related to thyroid hormone metabolism (deiodinases, dio1, dio2 and uridinediphosphate glucoronosyltransferases, ugt1ab), which might be responsible for the altered THs levels. However, the transcript of transthyretin (ttr) was significantly down-regulated at ≥ 3 μg/L of BPS, while the mRNA levels of thyroid hormone receptors (trα and trβ) and dio3 remained unchanged. All the results indicated that exposure to BPS altered the whole-body THs and TSH concentrations and changed the expression profiling of key genes related to HPT axis, thus triggering thyroid endocrine disruption.

Curcumin induces G2/M arrest, apoptosis, NF-κB inhibition, and expression of differentiation genes in thyroid carcinoma cells

The therapy of unresectable advanced thyroid carcinomas shows unfavorable outcome. Constitutive nuclear factor-κB (NF-κB) activation in thyroid carcinomas frequently contributes to therapeutic resistance; the radioiodine therapy often fails due to the loss of differentiated functions in advanced thyroid carcinomas. Curcumin is known for its anticancer properties in a series of cancers, but only few studies have focused on thyroid cancer. Our aim was to evaluate curcumin's molecular mechanisms and to estimate if curcumin could be a new therapeutic option in advanced thyroid cancer. Human thyroid cancer cell lines TPC-1 (papillary), FTC-133 (follicular), and BHT-101 (anaplastic) were treated with curcumin. Using real-time PCR analysis, we investigated microRNA (miRNA) and mRNA expression levels. Cell cycle, Annexin V/PI staining, and caspase-3 activity analysis were performed to detect apoptosis. NF-κB p65 activity and cell proliferation were analyzed using appropriate ELISA-based colorimetric assay kits. Treatment with 50μM curcumin significantly increased the mRNA expression of the differentiation genes thyroglobulin (TG) and sodium iodide symporter (NIS) in all three cell lines and induced inhibition of cell proliferation, apoptosis, and decrease of NF-κB p65 activity. The miRNA expression analyses showed a significant deregulation of miRNA-200c, -21, -let7c, -26a, and -125b, known to regulate cell differentiation and tumor progression. Curcumin arrested cell growth at the G2/M phase. Curcumin increases the expression of redifferentiation markers and induces G2/M arrest, apoptosis, and downregulation of NF-κB activity in thyroid carcinoma cells. Thus, curcumin appears to be a promising agent to overcome resistance to the conventional cancer therapy.

Association of the Asp1312Gly Thyroglobulin Gene Polymorphism with Susceptibility to Differentiated Thyroid Cancer in an Iranian Population

Background and aim:While the causes of thyroid cancer in most patients remain largely unknown, it has recently been reported that there may be links to particular chromosome regions. In particular, polymorphisms (SNPs) in the thyroglobulin (TG) gene could be susceptibility factors.Methods:In this case-control study, any association of the Asp1312Gly single nucleotide polymorphism (SNP) in the TG gene (rs2069556) with susceptibility to differentiated thyroid cancer (DTC) was investigated among 103 Iranian patients and 100 controls who had no history of any type of cancer. Genomic DNA was extracted from the whole blood by salting out procedure. High Resolution Melting (HRM) technique was used to detect this SNP.Results:Data were analyzed with SPSS software and the results showed that the recessive GG genotype was associated with an increased risk of differentiated thyroid carcinoma when compared to the AA+AG genotypes (OR: 2.06; CI: 1.09-3.89; P-value: 0.025).Conclusion:Although our study demonstrated that differentiated thyroid cancer is significantly associated with this polymorphism, further studies with larger populations are required to confirm our findings.

Advances and Perspectives in Genetics of Congenital Thyroid Disorders Associated with Thyroglobulin Gene Mutations

Dyshormonogenesis due to thyroglobulin (TG) gene mutations is a rare cause of congenital hypothyroidism with an estimated incidence of approximately 1 in 100,000 newborns.