SOX2, JAGGED1, ß-Catenin, and Vitamin D Receptor Expression Patterns during Early Development and Innervation of the Human Inner Ear.

Sensorineural hearing loss can be caused by lesions to the inner ear during development. Understanding the events and signaling pathways that drive inner ear formation is crucial for determining the possible causes of congenital hearing loss. We have analyzed the innervation and expression of SOX2, JAGGED1, ß-catenin (CTNNB1), and vitamin D receptor (VDR) in the inner ears of human conceptuses aged 5 to 10 weeks after fertilization (W) using immunohistochemistry. The prosensory domains of the human inner ear displayed SOX2 and JAGGED1 expression throughout the analyzed period, with SOX2 expression being more extensive in all the analyzed timepoints. Innervation of vestibular prosensory domains was present at 6 W and extensive at 10 W, while nerve fibers reached the base of the cochlear prosensory domain at 7-8 W. CTNNB1 and VDR expression was mostly membranous and present during all analyzed timepoints in the inner ear, being the strongest in the non-sensory epithelium. Their expression was stronger in the vestibular region compared to the cochlear duct. CTNNB1 and VDR expression displayed opposite expression trends during the analyzed period, but additional studies are needed to elucidate whether they interact during inner ear development.

Role of ST6GAL1 in Thyroid Cancers: Insights from Tissue Analysis and Genomic Datasets.

Thyroid cancer is the predominant endocrine-related malignancy. ST6 ß-galactoside α2,6-sialyltransferase 1 (ST6GAL1) has been studied in various types of cancers; however, the expression and function of ST6GAL1 in thyroid cancer has not been investigated so far. Previously, we conducted two genome-wide association studies and have identified the association of the ST6GAL1 gene with plasma thyroglobulin (Tg) levels. Since Tg levels are altered in thyroid pathologies, in the current study, we wanted to evaluate the expression of ST6GAL1 in thyroid cancer tissues. We performed an immunohistochemical analysis using human thyroid tissue from 89 patients and analyzed ST6GAL1 protein expression in papillary thyroid cancer (including follicular variant and microcarcinoma) and follicular thyroid cancer in comparison to normal thyroid tissue. Additionally, ST6GAL1 mRNA levels from The Cancer Genome Atlas (TCGA, n = 572) and the Genotype-Tissue Expression (GTEx) project (n = 279) were examined. The immunohistochemical analysis revealed higher ST6GAL1 protein expression in all thyroid tumors compared to normal thyroid tissue. TCGA data revealed increased ST6GAL1 mRNA levels in both primary and metastatic tumors versus controls. Notably, the follicular variant of papillary thyroid cancer exhibited significantly higher ST6GAL1 mRNA levels than classic papillary thyroid cancer. High ST6GAL1 mRNA levels significantly correlated with lymph node metastasis status, clinical stage, and reduced survival rate. ST6GAL1 emerges as a potential cancer-associated glycosyltransferase in thyroid malignancies, offering valuable insights into its diagnostic and prognostic significance.

Evaluation of Correlations Between Food-Specific Antibodies and Clinical Aspects of Hashimoto's Thyroiditis.

OBJECTIVE: We have comprehensively evaluated an immunologic response to food antigens, mediated by immunoglobulin G (IgG) antibodies, on clinical aspects of Hashimoto's thyroiditis (HT). METHODS: IgG antibodies to 125 food antigens were measured in serum samples of 74 HT patients and 245 controls using microarray-based enzyme-linked immunosorbent assay (ELISA) test. We analyzed differences in IgG levels between two groups and evaluated correlations between food-specific IgG levels and HT-related clinical phenotypes (thyroid hormones/antibodies, symptoms of hypothyroidism, measures of body size and blood pressure) and food consumption in HT patients. RESULTS: We observed increased IgG levels to 12 different food antigens in either HT cases or controls, of which plum-specific IgG antibodies were significantly higher (p = 1.70 × 10-8), and almond-specific IgG antibodies were significantly lower (p = 8.11 × 10-5) in HT patients in comparison to controls, suggesting their possible roles in HT etiology or symptomatology. There was no significant correlation between any of 12 increased food-specific IgG antibodies, along with gluten-specific IgG, with clinically important phenotypes, such as thyroid hormones/antibodies or symptoms. Among other tested correlations, the most interesting is the negative correlation between coffee and tea combined IgG levels and number of symptoms, suggesting possible beneficial effect of tea and coffee on disease symptoms. We also found that food consumption is not correlated with IgG levels. CONCLUSIONS: Distribution of food-specific IgG antibodies is comparable between HT patients and controls, with the exception of plum and almond. There is no evidence that increased food-specific IgG antibodies are associated with clinical aspects of HT. Clarification of biology behind formation of these antibodies is needed.

Associations between vitamin D levels and dietary patterns in patients with Hashimoto's thyroiditis.

Introduction: Vitamin D insufficiency is a global health problem affecting healthy and diseased individuals, including patients with Hashimoto's thyroiditis (HT). Identifying dietary factors that may affect vitamin D levels and providing dietary guidelines accordingly can alleviate this problem. We therefore aimed to identify still unknown associations of dietary patterns, assessed through the Food Frequency Questionnaire (FFQ) with vitamin D blood levels. Materials and methods: FFQ was collected from 459 patients from Croatian Biobank of Patients with Hashimoto's thyroiditis (CROHT), while total 25(OH)D was measured from their stored serum samples. We performed linear regression analysis between vitamin D levels and weekly intake of 24 food groups in 459 patients with HT (ALL), and in two disease-severity groups (MILD and OVERT). Results: The main results of our study are observations of: (1) an inverse association between vitamin D levels and coffee consumption (ALL: ß = -0.433, p = 0.005; OVERT: ß = -0.62, p = 0.008); (2) an inverse association between vitamin D levels and sweets consumption (ALL: ß = -0.195, p = 0.034; OVERT: ß = -0.431, p = 0.006); (3) positive association between vitamin D levels and vegetable consumption (ALL: ß = 0.182, p = 0.019; OVERT, ß = 0.311, p = 0.009). Importantly, effect sizes of all three associations were more prominent in HT patients with prolonged and more severe disease (OVERT). Conclusion: Further research into the functional and causal relationships of the observed associations is important to provide guidance regarding coffee/sugar intake on vitamin D status. A well-balanced diet can help prevent vitamin D deficiency and improve the quality of life of patients with HT, especially those in later stages of disease characterized by greater metabolic imbalance.

Rs7537605 polymorphism in VAV3 gene and rs28665122 polymorphism in SEPS gene are not associated with Hashimoto's thyroiditis in North-East Algerian population.

Background: Hashimoto's thyroiditis (HT) is the most common form of autoimmune thyroid disease which leads, in most cases, to hypothyroidism. HT is also classified as a multifactorial disease, which is caused by an interaction between genetic and environmental factors. Current knowledge of HT genetics is still very limited, especially in Algerian population. Objective: We wanted to investigate the association of two single-nucleotide polymorphisms (SNPs) inside VAV3 and SEPS genes with HT in Algerian population. Methods: We conducted a case-control study that included 100 HT cases and 126 healthy controls that were recruited from three private endocrinology clinics. Two SNPs, rs7537605 and rs28665122 inside VAV3 and SEPS genes were genotyped using real-time polymerase chain reaction (real-time PCR). Binary logistic regression model was used to test the association of selected SNs with HT and linear regression model was used to test association of these SNPs with thyroid peroxidase antibodies (TPOAb) levels. Results: Binary logistic regression results revealed no allelic association of the minor allele A between Hashimoto's thyroiditis cases and healthy controls (P=0.896) for the rs7537606 in VAV3 gene. The same observation was reported for the AA (P=0.477), AG (P=0.752) genotypes and for the genotypic models: dominant (P=1.0) and recessive (P=0.555). Also, there was no significant difference in the TT (P=0.230), TC (P=0.717) and allelic distribution of the minor allele T (P=0.859), and the combined models: TT + TC (P=1.0), TC + CC (P=0.138) between patients and controls for the rs28665122 polymorphism of the SEPS1 gene. Conclusion: This is the first genetic study that investigated the genetic association of rs7537605 and rs28665122 inside VAV3 and SEPS genes in Algerian population. Our results suggest that these two SNPs may not be involved in the pathogeneses of HT since we found no association between them and HT/TPOAb levels. Further research that will include larger sample size is required.

Vitamin D and Hashimoto's Thyroiditis: Observations from CROHT Biobank.

The aims of this study were to evaluate: (1) associations of vitamin D with the presence/severity of Hashimoto's thyroiditis (HT) and (2) correlations of vitamin D with thyroid-related phenotypes. Total 25(OH)D (vitamin D in the text) was measured from stored serum samples of 461 HT patients and 176 controls from a Croatian Biobank of HT patients (CROHT). (1) Vitamin D levels, and proportions of vitamin D deficiency, were compared between HT cases and controls. HT patients were additionally divided into two groups (MILD and OVERT) to take into account HT severity. (2) Correlations between vitamin D and 10 clinical phenotypes in all HT patients and two subgroups of HT patients were tested using the Spearman correlation test. Our analyses were adjusted for age, gender, BMI, smoking status and seasonality of blood sampling. (1) No significant differences in vitamin D levels, or proportions of vitamin D deficiency, were detected between HT patients of all disease stages and controls. However, a nominally significant difference in vitamin D levels between MILD and OVERT subgroups (OR = 1.038, p = 0.023) was observed. Proportions of individuals with vitamin D deficiency during winter-spring were high: all HT cases (64.69%), MILD (60.64%), OVERT (68.7%), controls (60.79%). (2) A nominally significant negative correlation between vitamin D and TSH in all HT patients (r = -0.113, p = 0.029) and a positive correlation between vitamin D and systolic blood pressure in OVERT HT patients (r = 0.205, p = 0.025) were identified. Our study indicates that there is no association between vitamin D and HT; however, there may be a subtle decrease in vitamin D levels associated with overt hypothyroidism.

AATF and SMARCA2 are associated with thyroid volume in Hashimoto's thyroiditis patients.

Thyroid volume of Hashimoto's thyroiditis (HT) patients varies in size over the course of disease and it may reflect changes in biological function of thyroid gland. Patients with subclinical hypothyroidism predominantly have increased thyroid volume whereas patients with more pronounced hypothyroidism have smaller thyroid volumes. Suggested mechanism for thyroid atrophy is thyrocyte death due to apoptosis. We performed the first genome-wide association study (GWAS) of thyroid volume in two groups of HT patients, depending on levothyroxine (LT4) therapy, and then meta-analysed across. Study included 345 HT patients in total and 6 007 322 common autosomal genetic variants. Underlying hypothesis was that genetic components that are involved in regulation of thyroid volume display their effect in specific pathophysiologic conditions of thyroid gland of HT patients. We additionally performed immunohistochemical analysis using thyroid tissues and analysed differences in expression levels of identified proteins and apoptotic marker between HT patients and controls. We found genome-wide significant association of two loci, both involved in apoptosis, with thyroid volume of HT patients: rs7212416 inside apoptosis-antagonizing transcription factor AATF (P = 8.95 × 10-9) and rs10738556 near chromatin-remodeling SMARCA2 (P = 2.83 × 10-8). In immunohistochemical analysis we observed that HT patients with homozygous AATF risk genotypes have decreased AATF expression (0.46-fold, P < 0.0001) and increased apoptosis (3.99-fold, P = 0.0001) in comparison to controls. HT patients with heterozygous SMARCA2 genotypes have decreased SMARCA2 expression, albeit without reaching statistical significance (1.07-fold, P = 0.5876), and significantly increased apoptosis (4.11-fold, P < 0.0001). By two lines of evidence we show that two highly plausible genetic loci, AATF and SMARCA2, may be involved in determining the thyroid volume of HT patients. The results of our study significantly add to the current knowledge of disturbed biological mechanisms in thyroid gland of HT patients.

Differences in food consumption between patients with Hashimoto's thyroiditis and healthy individuals.

Food is considered as important environmental factor that plays a role in development of Hashimoto's thyroiditis (HT). The goal of our study was to identify food groups, assessed by food frequency questionnaire, that differ in consumption frequency between 491 patients with HT and 433 controls. We also analysed association of food groups with the wealth of HT-related clinical traits and symptoms. We found significantly increased consumption of animal fat (OR 1.55, p < 0.0001) and processed meat (OR 1.16, p = 0.0012) in HT cases, whereas controls consumed significantly more frequently red meat (OR 0.80, p < 0.0001), non-alcoholic beverages (OR 0.82, p < 0.0001), whole grains (OR 0.82, p < 0.0001) and plant oil (OR 0.87, p < 0.0001). We also observed association of plant oil consumption with increased triiodothyronine levels in HT patients (ß = 0.07, p < 0.0001), and, association of olive oil consumption with decreased systolic blood pressure (ß = - 0.16, p = 0.001) in HT patients on levothyroxine (LT4) therapy. Analysis of food consumption between HT patients with and without LT4 therapy suggest that patients do not tend to modify their diet upon HT diagnosis in our population. Our study may be of relevance to nutritionists, nutritional therapists and clinicians involved in developing dietary recommendations for HT patients.