Risk Of Hashimoto's Thyroiditis Research Articles

Causal role of immune cells in Hashimoto's thyroiditis: Mendelian randomization study.

Hashimoto's thyroiditis (HT) is a common autoimmune disease whose etiology involves a complex interplay between genetics and environment. Previous studies have demonstrated an association between immune cells and HT. However, the casual relationship was not clear. We aimed to explore the causal associations between signatures of immune cells and HT. In this study, bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate the potential causal relationship between 731 immune cell signatures and HT by using genome-wide association study (GWAS) data. Heterogeneity and horizontal pleiotropy were detected through extensive sensitivity analyses. The increased levels of six immune phenotypes were observed to be causally associated with increased risk of HT P < 0.01, which were CD3 on CM CD8br, CD3 on CD39+ secreting Treg, HLA DR on CD33dim HLA DR+ CD11b-, CD3 on CD4 Treg, CD62L- plasmacytoid DC %DC, and CD3 on CD45RA+ CD4+. In addition, the levels of FSC-A on HLA DR+ T cell and CD62L on monocyte were associated with disease risk of HT P < 0.01. In addition, HT also had causal effects on CD3 on CM CD8br, CCR2 on monocyte, CD25 on CD39+ resting Treg, and CCR2 on CD62L+ myeloid DC P < 0.05. In this study, we demonstrated the genetic connection between immune cell traits and HT, thereby providing guidance and direction for future treatment and clinical research.

Autoimmune Thyroiditis and Vitamin D.

Hashimoto's thyroiditis (HT) is marked by self-tissue destruction as a consequence of an alteration in the adaptive immune response that entails the evasion of immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review of the relationship between vitamin D status and HT and the role of vitamin D supplementation in reducing HT risk by modulating the immune system. There is extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titers decreased significantly. Further knowledge of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases requires the execution of additional randomized, double-blind, placebo-controlled trials and longer follow-up periods.

Treg cells as a protective factor for Hashimoto`s thyroiditis: a Mendelian randomization study.

Hashimoto's thyroiditis (HT), a chronic autoimmune disorder impacting thyroid function, is a growing public health concern. The relationship between Treg cells and HT has been extensively studied, with Treg cells considered crucial in suppressing HT progression. However, these studies have mainly been observational, limiting our understanding of Treg cells' impact on HT risk. Leveraging large datasets, we utilized Mendelian randomization (MR) analysis to examine the causal association between Treg cell biomarkers and HT, providing additional validation for these relationships. Comprehensive two-sample Mendelian randomization analysis was performed to determine the causal association between Treg cells signatures and HT in this study. Based on publicly available genetic data, we explored causal associations between 165 Treg cells signatures and HT risk. The European cohort study has identified five Treg cell phenotypes that causally protect against HT risk. Resting Treg %CD4 (OR = 0.975, 95% CI = 0.954~0.998, P = 0.030); CD4 on resting Treg (OR = 0.938, 95% CI = 0.882~0.997, P = 0.041; CD28- CD8dim %CD8dim (OR = 0.983, 95% CI = 0.969~0.998, P = 0.030); CD25 on CD39+ resting Treg (OR = 0.926, 95% CI = 0.864~0.991, P = 0.026); 5) CD28 on activated & secreting Treg (OR = 0.969, 95% CI = 0.942~0.996, P = 0.025). The Asian cohort study has identified four Treg cell phenotypes negatively correlated with the risk of HT. CD25hi %T cell (OR = 0.635, 95% CI = 0.473~852, P = 0.002); CD4 Treg %CD4 (OR = 0.829, 95% CI = 0.687~1.000, P = 0.050); CD127-CD8br %T cell (OR = 0.463, 95% CI =0.311~0.687, P< 0.001); CD3 on resting Treg (OR = 0.786, 95% CI = 0.621~0.994, P = 0.044). Our study has demonstrated the close connection between Treg cells and HT by genetic means, thus providing foundational basis for future research.

Prediction and Classification models for Hashimoto's thyroiditis risk using clinical and paraclinical data

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The association between dietary selenium intake and Hashimoto's thyroiditis among US adults: National Health and Nutrition Examination Survey (NHANES), 2007-2012.

Selenium has been shown to influence the pathological processes and physiological functions of thyroid. Although growing evidence has shown that selenium can improve the treatment of Hashimoto's thyroiditis (HT), there is a need to evaluate the association between dietary selenium intake and HT in a large cross-sectional study. This study explored the association between dietary selenium intake and HT based on the National Health reand Nutrition Examination Survey (NHANES) database (2007-2012). A total of 8756 of 30,442 participants were included in the study. Dietary selenium intake was the independent variable, while HT was the dependent variable. In addition, the relative importance of the selected variables was determined using the XGBoost model. A smooth curve was constructed based on the fully adjusted model to investigate the potential linear relationship between dietary selenium intake and HT. Smooth curves were also constructed to explore the linear/non-linear relationship between dietary selenium intake and thyroid peroxidase antibody (TPOAb)/ thyroglobulin antibody (TgAb). The mean age of the enrolled participants was 44.35years (± 20.92). The risk of HT was significantly reduced by a 35% per-unit increase in dietary selenium intake after fully adjusting for covariates according to the model (log2-transformed data; OR 0.65; 95% CI 0.51, 0.83). The XGBoost model revealed that dietary selenium intake was the most important variable associated with Hashimoto's thyroiditis. Dietary selenium intake (Log2-transformed) was negatively correlated with TPOAb levels [-16.42 (-22.18, -10.65), P < 0.0001], while a non-linear relationship was observed between dietary selenium intake and TgAb with an inflection point of 6.58 (95.67μg, Log2-transformed). Dietary selenium intake is independently and inversely associated with HT risk. Moreover, dietary selenium intake is negatively correlated with TPOAb levels and non-linearly correlated with TGAb levels. Therefore, dietary selenium intake may be a safe and low-cost alternative for the prevention and treatment of HT.

Gender-Specific Impact of Metabolic Obesity Phenotypes on the Risk of Hashimoto's Thyroiditis: A Retrospective Data Analysis Using a Health Check-Up Database.

BackgroundHashimoto’s thyroiditis (HT) is recognized as the most common autoimmune thyroid disease, often accompanied by the diffuse enlargement of thyroid with abundant blood flow and elevated level of thyroid autoantibodies. As obesity had a positive association with the risk of HT. Thus, this retrospective study was established to further explore the gender relationship between metabolic obesity phenotypes and the risk of Hashimoto’s thyroiditis (HT).Materials and MethodsData for 3697 subjects aged ≥18 years were randomly collected from a Health check-up database from April to December 2019. Obesity was defined by general obesity (GO; body mass index [BMI] ≥28 kg/m2) and abdominal obesity (AO; waist circumstance, male ≥90 cm, female ≥85 cm). Metabolic unhealthy was defined as having at least one metabolic syndrome component and a homeostasis model assessment of insulin resistance ≥2.5. Obesity phenotypes were divided into three groups: GO, AO, compound obesity (GO+AO). After adjustment for potential confounding factors, multivariate logistic regression was used to assess the association between metabolic obesity phenotypes and risk of HT by sex and explore the correlation between different obesity patterns and HT risk by metabolic health status.ResultsThe incidence of HT was 23.5% and significantly higher among females than males with different metabolic phenotypes (26.2% vs 20.5%, p<0.05), except metabolically healthy AO. Compared with non-obese subjects, different metabolic obesity phenotypes were independent risk factors among males (p<0.05). Among females, unhealthy metabolic status with GO (adjusted odds ratio [OR]=2.62) or AO (adjusted OR=2.87) and metabolically healthy non-GO (adjusted OR=2.05) were risk factors of HT (p<0.05). Increasing BMI categories and waist circumstance quartiles were positively correlated with HT risk (p for trend <0.05). Subgroup analyses indicated that GO+AO (adjusted OR=2.52) or only AO (adjusted OR=2.41) were risk factors for HT for those with unhealthy metabolic status. Moreover, GO+AO (adjusted OR=2.37) was an independent risk factor for HT under healthy metabolic status.ConclusionGO+AO was associated with an increased risk of HT, identifying higher BMI/WC as a significant risk factor for HT. Males with unhealthy metabolic state or obesity and metabolically unhealthy females with obesity are high-risk group for HT. Additionally, only AO and GO+AO conferred increased risk of HT for individuals with metabolic abnormalities.

Familial Risk of Hashimoto's Thyroiditis Among First-Degree Relatives: A Population-Based Study in Korea.

Background: Few small-scale studies have reported a genetic and familial predisposition in Hashimoto's thyroiditis (HT), however, quantified familial risk estimates from population-level data are unavailable. We aimed to estimate the incidence and familial risk of HT among first-degree relatives (FDR) according to age, sex, and family relationships. Methods: We conducted a population-based study in the general population of Korea from 2002 to 2017. Using the nationwide health insurance database, which has full population coverage and family relationship information, a cohort of 22 million individuals with blood-related FDR comprising 12 million families were followed up for a familial occurrence of HT. Age- and sex-adjusted incidence risk ratios (IRRs) were calculated in individuals with an affected FDR compared with those without an affected FDR. Results: Among 21,940,795 individuals, 234,912 had an HT-affected FDR, of whom 2425 familial cases developed HT with an incidence of 7.12/10,000 person-years. The familial risk for HT was 6.5-fold (95% confidence interval [CI]: 6.24-6.78) higher in individuals with versus without affected FDR. According to relationship, familial risks were IRR 102.71, IRR 7.80, IRR 5.54, and IRR 5.52 with an affected twin, sibling, mother, and father, respectively, and the corresponding incidence (/10,000 person-years) was 115.57, 10.66, 5.73, and 5.91. Same-sex twins had three times higher risk of developing HT than opposite-sex twins (IRR 121.01 vs. 21.46). The sex-specific familial risk was higher in males than females. The risks demonstrated age dependence, being higher in younger age groups. Conclusions: This study represents the largest population-based study of familial HT risk in Asia. We demonstrated elevated familial risk of incident HT among FDR, but with lower magnitude as those observed in previous studies. Familial risk increased with the degree of genetic relatedness among FDR indicating a prominent role of genetic factors in the familial aggregation of HT. Elevated risks in the younger age groups should motivate clinicians to screen people with a family history, especially those <30 years.

Correlation Analysis of Th17/Treg Cells and PTPN22 Gene Polymorphism in HT Patients with Different Iodine Nutritional Status

Background: The incidence of Hashimoto's thyroiditis (HT) may be related to environmental, immune, and genetic factors. Different iodine nutritional status can affect thyroid function. Th17/Treg cell imbalance is involved in the pathogenesis of autoimmune thyroid diseases, and PTPN22 is an important susceptibility gene related to autoimmune diseases. To study the relationship between Th17/Treg cells and cytokines and PTPN22 gene polymorphism in HT patients with different iodine nutritional status is to determine the role of immune and genetic factors in the pathogenesis of HT. Objective: To investigate the correlation between Th17/Treg cells and factors protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene-1123G>C site (rs2488457) polymorphism in peripheral blood mononuclear cells (PBMC) of Hashimoto's thyroiditis (HT) patients with different iodine nutritional status. Methods: 100 HT patients and 60 healthy subjects in Cang Zhou are selected from 2019 to 2020. Flow cytometry and real-time fluorescent quantitative PCR are used to detecting the proportion and ratio of Th17 and Treg cells in PBMC, as well as retinoic acid-related orphan receptor-γt (ROR-γt) and fork head/winged spiral transcription factor 3 (Foxp3) mRNA expression levels. Single allele-specific primer-polymerase chain reaction (SASP-PCR) technology is taken to sequence PTPN gene promoter-1123SNP leading to calculate the gene Type and allele frequency. Results: Th17 and Treg cells and factors in the PBMC of HT patients have a certain correlation with the-1123G>C locus of PTPN22 gene (rs2488457). The distribution frequency of rs2488457 genotype is consistent with Hardy Weinberg's law of genetic equilibrium. The distribution frequencies of various genotypes and alleles are significantly different between HT patients and the control group (P<0.05). PTPN22 gene-1123G>C site C/G, C/C genotype can increase of the risk of HT, while G/G genotype can decrease of the risk of HT. In Conclusion: The polymorphism of rs2488457 is related to susceptibility to HT. Carrying C/G and C/C genotypes may be risk factors for HT, and G/G genotypes may be protective factors for HT, but it has nothing to do with iodine nutrition status.

Association of Hemorrhoids With Hashimoto's Thyroiditis and Associated Comorbidities: A Nationwide Population-Based Cohort Study.

Background: To evaluate the relationship between hemorrhoids and Hashimoto's thyroiditis (HT).Methods: Using Taiwan's Longitudinal Health Insurance Database, we compared the incident risk of HT between the study cohort (comprising patients with hemorrhoids) and the comparison cohort (comprising patients without hemorrhoids). Both cohorts were followed from index date until the date of HT diagnosis, withdrawal from the National Health Insurance program, or the end of 2015.Results: The study cohort and comparison cohort comprised 6,486 patients with hemorrhoids and 25,944 patients without, respectively. The mean follow-up time was ~3 years. The incidence rate of HT in the study cohort was 5.37 per 1,000 person-years, which was higher than that of the control cohort (2.46 per 1,000 person-years). The risk of developing HT in the study cohort was 2.06 times (95% confidence interval [CI] = 1.02, 4.19) higher than that in the comparison cohort.Conclusion: In our study, patients with hemorrhoids could be at increased risk of HT compared with patients with other comorbidities of HT, such as cardiovascular disease.

Hashimoto's thyroiditis might increase polycystic ovary syndrome and associated comorbidities risks in Asia.

BackgroundTo investigate whether increased the comorbidities such as coronary artery disease (CAD) and risks between Hashimoto’s thyroiditis (HT) and polycystic ovary syndrome (PCOS) in Taiwanese women.MethodsPatients newly diagnosed as having HT during 2000–2012 were assigned to the case group. Cases and controls were matched for age and comorbidities at a 1:2 ratio using propensity score matching. Incidence was calculated in the unit of 1000 person-year. Univariate and multivariate Cox proportional hazard regression, multivariate Cox, logistic regression, and Kaplan-Meier analyses were performed.ResultsAmong 3,996 participants, 2,664 constituted the control group and 1,332 constituted the case group. The PCOS risk in patients with HT increased by 2.37 times [95% confidence interval (CI): 1.22–4.62] compared with the controls. Hypertension (HTN) [adjusted odds ratio (OR): 1.31, 95% CI: 1.03–1.66] and hyperlipidemia (adjusted OR: 1.55, 95% CI: 1.2–1.9) were more common in HT patients without PCOS than in other patients. The adjusted OR for CAD in patients with HT was 1.51 (95% CI: 1.11–2.06), whereas that in patients with HT and PCOS was 5.92 (95% CI: 1.32–26.53).ConclusionsIn our study, the PCOS risk in patients with HT increased by 2.37 times, which is lower than the increase in HT risk in Asian patients with PCOS (4.56 times). The proportion of CAD increased significantly by 5.92 times in patients with HT and PCOS compared with patients with HT only.

Association of CTLA4 (rs4553808) and PTPN22 (rs2476601) gene polymorphisms with Hashimoto's thyroiditis disease: A case-control study and an In-silico analysis

In addition to other factors regarding the disease susceptibility, genetic factors are the main causes of Hashimoto's thyroiditis (HT) disease. CTLA4 and PTPN22 are the most prominent genes involved in the immune system regulation, thus effective in the pathogenesis of autoimmune diseases. In the current study, the association of two polymorphisms of CTLA4 and PTPN22 genes, 1661A/G (CTLA-4 gene) and C1858T (PTPN22 gene), with HT was investigated by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) technique. The effects of -1661A/G and C1858T polymorphisms on the mRNA and protein structures of CTLA-4 and PTPN22 were investigated by an in silico analysis. There was no significant difference between the genotype and allele frequencies of PTPN-22 gene polymorphism (rs2476601) in case and control groups. There was a positive association between the frequency of heterozygous genotype of CTLA4-1661A/G polymorphism (rs4553808) and HT (P = .04), but no association was seen regarding allele frequencies. In-silico analysis predicted that the transition of allele A to allele G would lead to the loss of some of the binding sites. Also, the structural analysis of C1858T transition effect on protein revealed a significant influence on PTPN-22 function. Our results showed that heterozygous genotype of -1661A/G CTLA4 gene variation might be related with the risk of HT.

Association of cytokine Th2 gene polymorphisms with autoimmune thyroid diseases in Tunisian population.

Autoimmune thyroid diseases (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are complex genetic diseases. Th2 cytokines act on the development of AITD. This study was conducted on Tunisian patients with AITD to investigate the association of Th2 cytokine gene polymorphisms and haplotype combination with GD or HT risk. A total of 156 controls, 160 patients with HT and 88 patients with GD were genotyped for IL-4 rs2243250, IL-5 rs2069812, IL-6 rs1800796 and IL-13 rs1800925 polymorphisms by PCR-RFLP. The AITD risk was assessed by a logistic regression analysis using the SNP stats statistical program. False-positive report probability (FPRP) was estimated to evaluate significant findings. IL-13 rs1800925 was associated with GD, after adjustment for age and gender, in codominant, dominant and allele genetic models (p=.0072; p=.0018; p=.012, respectively). Significant association of the IL-6 rs1800796C/G genotype with GD was also detected (p=.025). Furthermore, increased risk of HT was still found for IL-13 rs1800925T allele (p=.039, OR=1.39) and for IL-4 rs2243250T/T genotype both in codominant (p=.033, OR=2.59) and recessive (p=.011, OR=2.73) models after adjustment for age and gender. Interestingly, haplotype analysis performed on the IL-4, IL-5 and IL-13 genes revealed a high risk of HT with CTT haplotype (p=.008, OR=2.12). However, the CCT haplotype is a protective factor (OR=0.36). Patients carrying the CT haplotype with only one minor allele had a moderate risk of HT (OR=1.56). The FPRP analysis showed that the association of IL-13 rs1800925 polymorphism with GD and HT and the association of CTT haplotype with HT were noteworthy. In conclusion, the IL-4, IL-5, IL-6 and IL-13 polymorphism may play a role in susceptibility to GD and HT in the Tunisian population. Furthermore, gene-gene interaction between the IL-4, IL-5 and IL-13 significantly increases the risk of AITD. Further studies with larger numbers of individuals are needed to confirm the results.

Genetic Polymorphisms on 4q21.1 Contributed to the Risk of Hashimoto's Thyroiditis

Background: Hashimoto's thyroiditis (HT) is a common autoimmune disease characterized by lymphoid infiltration of the thyroid gland, including both T- and B-cells. Early studies have shown that HT is a complex disorder affected by both environmental and genetic factors. Recently, the single nucleotide polymorphism (SNP) rs2276886 associated with the CXCL9 gene was identified as associated with autoimmune thyroid disease susceptibility in Japanese populations. The aim of the present study was to validate this result for HT in a Chinese Han population. Methods: Study subjects, including 688 HT cases and 1456 healthy controls, were recruited, and 10 SNPs located within the CXCL9 gene were genotyped. Genetic association analyses were performed by fitting logistic models. Bioinformatics tools, including RegulomeDB and GTEx were utilized to investigate the functional consequences of the SNPs found to be significantly associated with HT. Results: SNP rs2276886 was identified as significantly associated with the risk of HT (odds ratio [OR] = 1.25, p = 0.0006). No significant expression quantitative trait loci (eQTL) signals could be identified for CXCL9. Significant eQTL signals were found for other genes, including ART3, CXCL10, CXCL11, NAAA, PPEF2, and SCARB2. This SNP physically maps to the CXCL9 gene region; however, further bioinformatic analyses indicated that this SNP might be associated with the gene NAAA. Conclusions: The rs2276886 SNP was found to be significantly associated with HT susceptibility. However, our findings suggest that this SNP which maps to the chromosomal region 4q21.1 likely effects the NAAA gene (as opposed to the CXCL9 gene), but still contributes to the susceptibility to HT in Han Chinese populations.

Interaction of Genetic Variations in NFE2L2 and SELENOS Modulates the Risk of Hashimoto's Thyroiditis.

Background: Several single-nucleotide polymorphisms (SNPs) are known to increase the risk of Hashimoto's thyroiditis (HT); such SNPs reside in thyroid-specific genes or in genes related to autoimmunity, inflammation, and/or cellular defense to stress. The transcription factor Nrf2, encoded by NFE2L2, is a master regulator of the cellular antioxidant response. This study aimed to evaluate the impact of genetic variation in NFE2L2 on the risk of developing HT.Methods: In a case–control candidate gene association study, functional SNPs in the NFE2L2 promoter (rs35652124, rs6706649, and rs6721961) were examined either as independent risk factors or in combination with a previously characterized HT risk allele (rs28665122) in the gene SELENOS, encoding selenoprotein S (SelS). A total of 997 individuals from the north of Portugal (Porto) were enrolled, comprising 481 HT patients and 516 unrelated healthy controls. SELENOS and NFE2L2 SNPs were genotyped using TaqMan® assays and Sanger sequencing, respectively. Odds ratios (ORs) were calculated using logistic regression, with adjustment for sex and age. Expression of SelS was analyzed by immunohistochemistry in thyroid tissue from HT patients and control subjects. Molecular interactions between the Nrf2 and SelS pathways were investigated in thyroid tissues from mice and in rat PCCL3 thyroid follicular cells.Results: When all three NFE2L2 SNPs were considered together, the presence of one or more minor alleles was associated with a near-significant increased risk (OR = 1.43, p = 0.072). Among subjects harboring only major NFE2L2 alleles, there was no increased HT risk associated with heterozygosity or homozygosity for the SELENOS minor allele. Conversely, in subjects heterozygous or homozygous for the SELENOS risk allele, the presence of an NFE2L2 minor allele significantly increased HT risk by 2.8-fold (p = 0.003). Immunohistochemistry showed reduced expression of SelS in thyroid follicular cells of HT patients. In Nrf2 knockout mice, there was reduced expression of SelS in thyroid follicular cells; conversely, in PCCL3 cells, reducing SelS expression caused reduced activity of Nrf2 signaling.Conclusions: The NFE2L2 promoter genotype interacts with the SELENOS promoter genotype to modulate the risk of HT in a Portuguese population. This interaction may be due to a bidirectional positive feedback between the Nrf2 and SelS pathways.

Thyroid function in Klinefelter syndrome: a multicentre study from KING group.

The prevalence and the etiopathogenesis of thyroid dysfunctions in Klinefelter syndrome (KS) are still unclear. The primary aim of this study was to evaluate the pathogenetic role of hypogonadism in the thyroid disorders described in KS, with the scope to distinguish between patients with KS and hypogonadism due to other causes (Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, iatrogenic hypogonadism and acquired hypogonadotropic hypogonadism after surgical removal of pituitary adenomas) called non-KS. Therefore, we evaluated thyroid function in KS and in non-KS hypogonadal patients. This is a case-control multicentre study from KING group: Endocrinology clinics in university-affiliated medical centres. One hundred and seventy four KS, and sixty-two non-KS hypogonadal men were enrolled. The primary outcome was the prevalence of thyroid diseases in KS and in non-KS. Changes in hormonal parameters were evaluated. Exclusion criterion was secondary hypothyroidism. Analyses were performed using Student's t test. Mann-Whitney test and Chi-square test. FT4 was significantly lower in KS vs non-KS. KS and non-KS presented similar TSH and testosterone levels. Hashimoto's thyroiditis (HT) was diagnosed in 7% of KS. Five KS developed hypothyroidism. The ratio FT3/FT4 was similar in both groups. TSH index was 1.9 in KS and 2.3 in non-KS. Adjustment for differences in age, sample size and concomitant disease in multivariate models did not alter the results. We demonstrated in KS no etiopathogenic link to hypogonadism or change in the set point of thyrotrophic control in the altered FT4 production. The prevalence of HT in KS was similar to normal male population, showing absence of increased risk of HT associated with the XXY karyotype.

ASSOCIATION OF FOXP3 GENE VARIANTS WITH RISK OF HASHIMOTO'S THYROIDITIS AND CORRELATION WITH ANTI-TPO ANTIBODY LEVELS.

Regulatory T cells (Tregs) have critical roles in preventing autoimmune diseases such as Hashimoto's thyroiditis (HT). Forkhead box P3 (Foxp3), the master transcription factor of Tregs, plays a pivotal role in Treg function. Herein, we investigated the association of two single nucleotide polymorphisms (SNPs) of the Foxp3 gene with HT development. A total of 129 HT patients and 127 healthy subjects were genotyped for rs3761548 (-3279 A/C) and rs3761549 (-2383 C/T) in the Foxp3 gene, using polymerase chain reaction-restriction fragment length polymorphism. Genotypic and allelic distribution of rs3761548 SNP showed a significant association with HT. The CC genotype was observed in 37.2% of patients versus 22.1% of the controls [P<0.008, odds ratio (OR): 2.1; 95% confidence interval (CI): 1.2-3.6] and the AC genotype in 41.1% of patients compared to 54.3% of the controls (P<0.025, OR: 2.1; CI: 1.2-3.6). In addition, higher frequency of C allele in patients compared to controls (P=0.05, OR: 1.4; 95% CI: 0.9-2) suggested that patients with the CC genotype and C allele had increased susceptibility to HT. There were significantly higher serum levels of anti-thyroid peroxidase (ATPO) antibody in patients with the rs3761548 CC genotype (1156±163 IU/mL) compared to the other genotypes (≈582-656 IU/mL; P<0.004). We observed a greater frequency of the AC genotype in patients who had decreased ATPO antibody levels (P=0.02). The association of the rs3761548 SNP with risk of HT and its influence on ATPO antibody levels suggested an important role for Foxp3 in the biology and pathogenesis of HT.

Association of glutathione peroxidase 1 gene polymorphism (rs1050450) with Hashimoto's thyroiditis in Northwest Iran

Hashimoto's thyroiditis (HT) is an inflammatory and autoimmune thyroid disorder. The oxidative stress and inflammation crosstalk play pivotal role in the pathogenesis of HT. The activity of glutathione peroxidase-1 (GPx-1) enzyme is affected by single nucleotide polymorphism in the rs1050450 position, which influence the risk of several diseases. The aim of this study is to determine the association of rs1050450 genotype variant and the HT risk. A hundred and five patients HT patients were enrolled and DNA and serum were isolated from the whole blood, and used for genotyping and serum total antioxidant capacity (sTAC), determination of antibody titer and thyroid stimulating hormone (TSH) level assessment. The glutathione peroxidase-1 genotyping performed using polymerase chain reaction and restriction fragment length polymorphism with ApaI enzyme. The sTAC were measured by FRAP method. Anti-thyroid peroxidase antibody (anti-TPO) and TSH levels were measured via ELISA assay. The results indicated the sTAC in HT patients (30.32 ± 16.84 μmol/L) is significantly lower than healthy controls (44.39 ± 19.94 μmol/L). There is a significant association between the rs1050450 genotype and the HT risk. T allele frequency is higher in HT patients than healthy control groups while there is no significant difference in sTAC between three rs1050450 genotype (CC, CT and TT). The T allele is associated with higher anti-TPO levels (TT = 136.33 ± 82.27, CT = 308.40 ± 259.39, CC = 294.57 ± 309.54 IU/mL). We found a significant negative correlation between TSH and age of patients. The T allele in rs1050450 position of glutathione peroxidase-1 gene associated with higher HT risk independent from serum antioxidant power and may mediated by local antioxidant activity in thyroid gland microenvironment.

Associations Between Three CTLA-4 Polymorphisms and Hashimoto's Thyroiditis Risk: An Updated Meta-Analysis with Trial Sequential Analysis.

In this article, we conducted an updated meta-analysis with trial sequential analysis (TSA) to refine the associations between three common single nucleotide polymorphisms (SNPs) in the CTLA-4 gene (+49A/G, CT60, and -318C/T) and Hashimoto's thyroiditis (HT). Statistical association analyses were performed using four genetic models, including the allelic, codominant, dominant, and recessive models with the Revman 5.3, Stata 14.0, and TSA 0.9 software. For quality evaluation, the Newcastle-Ottawa Scale was used. Our meta-analysis included 29 independent studies with low risk of bias that involved 3614 cases and 8839 controls. The pooled results indicated a significant association between the +49A/G polymorphism and an increased risk of HT in all four genetic models. Furthermore, the TSA demonstrated that the evidence of this association was robust and credible. Subgroup analysis revealed a significantly higher risk of HT in Asians compared with Caucasians associated with the +49A/G polymorphism. Surprisingly, in contrast to the results with adults, we did not find any significant association when analyzing the pediatric subgroup. For the CT60 polymorphism, a significant association with risk of HT was detected overall, and subgroup analysis revealed that this association was significant in the Asian subgroup, but not in the Caucasian subgroup. No statistically significant associations were detected in any of the investigated genetic models for the -318C/T polymorphism. However, the results of the TSA suggested that the sample sizes used for the CTLA-4 CT60 and -318C/T SNPs were insufficient. Our meta-analysis showed significant associations between the risk of HT and both the +49A/G and CT60 polymorphisms, but not the -318C/T polymorphism. In addition, the TSA results indicated that CTLA-4 +49A/G should be considered as a biomarker for HT, whereas both the CT60 and -318C/T SNPs warrant confirmation by further studies.

A meta-analysis of Hashimoto's thyroiditis and papillary thyroid carcinoma risk.

ObjectiveIt remains inconclusive whether Hashimoto’s thyroiditis (HT) predisposes patients to the development of papillary thyroid carcinoma (PTC). We conducted a meta-analysis of the available data to address this question.ResultsTwenty-seven eligible studies were selected, including 18 archival thyroidectomy studies, 6 fine-needle aspiration (FNA) studies, and 3 selective FNA or thyroidectomy studies. A total of 76,281 patients, including 12,476 cases of thyroid cancer, were included in these studies. The mean rate of PTC among patients with HT ranged from 1.12% (selective FNA or thyroidectomy studies) to 40.11% (thyroidectomy studies). All three types of studies supported the correlation between HT and PTC. The overall pooled odds ratio (OR) of the PTC risk for HT (HT versus non-HT) was 2.12 (95% confidence interval [CI]: 1.78-2.52).MethodsWe searched all relevant published studies using the citation databases PubMed and Embase. The ORs and corresponding 95% CIs were calculated by the random-effects model for the association between HT and PTC.ConclusionsOur meta-analysis confirmed that HT predisposed patients to the development of PTC.

Hashimoto thyroiditis, anti-thyroid antibodies and systemic lupus erythematosus.

To study the prevalence of Hashimoto thyroiditis (HT), anti-thyroid autoantibodies (anti-thyroglobulin or TgAb and thyroperoxidase or TPOAb) in systemic lupus erythematosus (SLE) patients. To analyze if associated HT, TgAb and/or TPOAb influence clinical or serological profiles, disease activity and/or its cumulative damage. Three hundred and one SLE patients and 141 controls were studied for thyroid stimulating hormone, thyroxin, TgAb and TPOAb by chemiluminescence and immunometric assays. Patients' charts were reviewed for serological and clinical profiles. Activity was measured by SLE Disease Activity Index and cumulative damage by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for SLE. SLE patients were divided into: (i) with HT; (ii) with anti-thyroid antibodies but without HT; and (iii) without HT and without anti-thyroid antibodies, and were then compared. Furthermore, SLE patients were compared according to the number of positive anti-thyroid antibodies. Hashimoto thyroiditis prevalence in SLE was 12.6% and 5.6% in controls (P = 0.02; odds ratio = 2.4; 95% CI = 1.09-5.2). Lupus patients with HT had less malar rash (P = 0.02) and more anti-Sm (P = 0.04). Anti-Sm was more common in those with two anti-thyroid antibodies than in those with one or negative. The presence of HT or the number of positive autoantibodies did not associate either with disease activity (P = 0.95) or with cumulative damage (P = 0.98). There is a two-fold increased risk of HT in SLE patients. Anti-Sm antibodies favor this association and also double antibody positivity. Disease activity and cumulative damage are not related to HT or with autoantibodies.