scholarly journals Associations between CD160 polymorphisms and autoimmune thyroid disease: a case-control study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Weiwei He ◽  
Jing Zhao ◽  
Xuerong Liu ◽  
Sheli Li ◽  
Kaida Mu ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Autoimmune Thyroid Disease ◽  
Additive Model ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Dominant Model ◽  
Regression Analyses ◽  
Age And Gender ◽  
Autoimmune Thyroid ◽  
And Gender

Abstract Background Recent researches suggest that the CD160/HVEM/LIGHT/BTLA signaling pathway may contribute to the pathogeneses of autoimmune diseases, but the relationship between CD160 polymorphisms and autoimmune thyroid disease (AITD) has not been reported yet. This study aimed to evaluate the associations between CD160 polymorphisms and AITD. Methods A total of 1017 patients with AITD (634 Graves’ disease and 383 Hashimoto’s thyroiditis) and 856 unrelated healthy controls were recruited into our study. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated through logistic regression analyses. The CD160 SNPs were detected using Hi-SNP high-throughput genotyping. Results There was a statistically significant difference between Graves’ disease patients and the control group with respect to both the genotype distribution (P = 0.014) and allele frequency of rs744877 (P = 0.034). A significant association of CD160 rs744877 with AITD was observed before adjusted age and gender under a dominant model (OR = 0.79, 95%CI 0.66–0.95; P = 0.013) and an additive model (OR = 0.77, 95%CI 0.64–0.94, P = 0.008), and was also observed after adjusted age and gender under a dominant model (OR = 0.78, 95%CI 0.65–0.95; P = 0.011) and an additive model (OR = 0.76, 95%CI 0.63–0.93, P = 0.007). A significant association of rs744877 with Graves’ disease was observed under an allele model (OR = 0.84, 95%CI 0.71–0.98, P = 0.027), a dominant model (OR = 0.74, 95%CI 0.60–0.91; P = 0.005), and an additive model (OR = 0.72, 95%CI 0.58–0.90, P = 0.004). Multivariate logistic regression analyses suggested that the association remained significant after adjustment for age and gender. However, rs744877 was not related to Hashimoto’s thyroiditis. Furthermore, CD160 rs3766526 was not significantly related to either Graves’ disease or Hashimoto’s thyroiditis. Conclusion This is the first identification of the association of CD160 rs744877 with Graves’ disease. Our findings add new data to the genetic contribution to Graves’ disease susceptibility and support the crucial role of the CD160/HVEM/LIGHT/BTLA pathway in the pathogenesis of Graves’ disease.

scholarly journals Associations Between CD160 Polymorphisms and Autoimmune Thyroid Disease: A Case-Control Study

2020 ◽  
Author(s):  
Weiwei He ◽  
Jing Zhao ◽  
Xuerong Liu ◽  
Sheli Li ◽  
Kaida Mu ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Additive Model ◽  
Graves Disease ◽  
Dominant Model ◽  
Regression Analyses ◽  
Age And Gender ◽  
Autoimmune Thyroid ◽  
And Gender

Abstract Background/AimsRecent researches suggest that the CD160/HVEM/LIGHT/BTLA signaling pathway may contribute to the pathogeneses of autoimmune diseases, but the relationship between CD160 polymorphisms and autoimmune thyroid disease (AITD) has not been reported yet. This study aimed to evaluate the associations between CD160 polymorphisms and AITD.MethodsA total of 1017 patients with AITD (634 Graves' disease and 383 Hashimoto's thyroiditis) and 856 unrelated healthy controls were recruited into our study. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated through logistic regression analyses. The CD160 SNPs were detected using Hi-SNP high-throughput genotyping. ResultsThere was a statistically significant difference between Graves' disease patients and the control group with respect to both the genotype distribution (P=0.014) and allele frequency of rs744877 (P=0.034). A significant association of CD160 rs744877 with AITD was observed before adjusted age and gender under a dominant model (OR= 0.79, 95%CI 0.66-0.95; P= 0.013) and an additive model (OR= 0.77, 95%CI 0.64-0.94, P=0.008), and was also observed after adjusted age and gender under a dominant model (OR= 0.78, 95%CI 0.65-0.95; P= 0.011) and an additive model (OR= 0.76, 95%CI 0.63-0.93, P=0.007). A significant association of rs744877 with Graves' disease was observed under an allele model (OR= 0.84, 95%CI 0.71-0.98, P=0.027), a dominant model (OR= 0.74, 95%CI 0.60-0.91; P= 0.005), and an additive model (OR= 0.72, 95%CI 0.58-0.90, P=0.004). Multivariate logistic regression analyses suggested that the association remained significant after adjustment for age and gender. However, rs744877 was not related to Hashimoto's thyroiditis. Furthermore, CD160 rs3766526 was not significantly related to either Graves' disease or Hashimoto's thyroiditis.ConclusionThis is the first identification of the association of CD160 rs744877 with Graves' disease. Our findings add new data to the genetic contribution to Graves' disease susceptibility and support the crucial role of the CD160/HVEM/LIGHT/BTLA pathway in the pathogenesis of Graves' disease.

scholarly journals Associations between NLRC4 Gene Polymorphisms and Autoimmune Thyroid Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xuerong Liu ◽  
Xiaogang Bai ◽  
Jing Zhao ◽  
Chaoqun Gao ◽  
Peng Du ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Hashimoto's Thyroiditis ◽  
Genotype Distribution ◽  
Healthy Controls ◽  
Dominant Model ◽  
Autoimmune Thyroid Diseases ◽  
Age And Gender ◽  
Autoimmune Thyroid ◽  
And Gender ◽  
Allele Model

Background. Many studies have shown that NLRC4 inflammasome polymorphisms are associated with a variety of autoimmune diseases, but the associations between NLRC4 polymorphisms and autoimmune thyroid diseases (AITDs) are unclear. Our research was aimed at identifying the correlations between NLRC4 polymorphisms and AITDs. Methods. Hi-SNP high-throughput genotyping technology was used for detecting four single-nucleotide polymorphisms (SNPs) of NLRC4 in 1005 AITDs patients (including 629 Graves’ disease and 376 Hashimoto’s thyroiditis) and 781 healthy controls. Results. Compared with healthy controls, the allele frequencies and genotype distribution of rs385076 were statistically related to AITDs (P=0.016 and P=0.048, respectively) and Hashimoto’s thyroiditis (P=0.022 and P=0.046, respectively). Before adjusting for age and gender, rs385076 and AITDs had a significant association in three models of allele model, dominant model, and homozygous model. After adjusting for age and gender, in the above three models, there is still a clear relationship between them. Before adjusting for age and gender, there were prominent discrepancy between rs385076 and Hashimoto’s thyroiditis in the allele model (OR=0.81, 95% CI 0.67-0.97; P=0.021) and the dominant model (OR=0.73, 95% CI 0.57-0.94; P=0.014), after adjusting for age and gender, rs385076 and Hashimoto’s thyroiditis were significantly related to allele model, dominant model, and homozygous model. However, rs455060, rs212704, and rs675712 were not related to AITDs in our study. Conclusion. NLRC4 rs385076 was found to have a significant association with Hashimoto’s thyroiditis for the first time. It laid a foundation for the disclosure of the pathogenesis of AITDs, and provided a possible treatment prospect for HT.

scholarly journals Advances in Research on the Role of Chemokines in Occurrence and Development of Autoimmune Thyroid Disease

2015 ◽  
Vol 4 (3) ◽  
pp. 59-63
Author(s):  
Guang Ji
Keyword(s):  
Thyroid Disease ◽  
Hashimoto’S Thyroiditis ◽  
Autoimmune Thyroid Disease ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Neutrophil Chemotaxis ◽  
Autoimmune Thyroid

AbstractChemokines can be divided into four categories: α, β, γ, and δ. Chemokine α is related to neutrophil chemotaxis. Chemokine β is correlated with adsorption of monocytes, basophils, and eosinophils. Chemokine γ is mainly a lymphocyte chemokine. Function of chemokine δ remains unclear. Chemokines α and β are primarily related to occurrence and development of autoimmune thyroid disease. This study reviews chemokines and their receptors that are related to Graves’ disease and Hashimoto’s thyroiditis.

scholarly journals No association of two Fas gene polymorphisms with Hashimoto's thyroiditis and Graves' disease

2003 ◽  
pp. 393-396 ◽  
Author(s):  
BJ Stuck ◽  
MA Pani ◽  
F Besrour ◽  
M Segni ◽  
M Krause ◽  
...  
Keyword(s):  
Thyroid Disease ◽  
Genetic Risk ◽  
Hashimoto’S Thyroiditis ◽  
Gene Polymorphisms ◽  
Autoimmune Thyroid Disease ◽  
Fas Ligand ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Autoimmune Thyroid ◽  
Hla Dq

BACKGROUND: Apoptosis is a joint pathogenic process underlying autoimmune thyroid disease. Increased programmed cell death in thyrocytes causes hypothyroidism in Hashimoto's thyroiditis, whereas in Graves' disease infiltrating lymphocytes undergo apoptosis while thyrocytes appear to proliferate under protection of anti-apoptotic signals. The Fas/Fas ligand cascade represents a major pathway initiating apoptosis. Its role in autoimmunity is well studied and genetic polymorphisms in gene loci of Fas and its ligand have been shown to be associated with autoimmune diseases. OBJECTIVE: Due to the functional relevance of the Fas pathway in autoimmune thyroid disease we were interested in the possible contribution of polymorphisms in the Fas gene to the genetic risk of thyroid autoimmunity, which so far is mainly, but incompletely, attributed to the HLA DQ region and polymorphisms in the CTLA-4 gene. DESIGN: We genotyped Caucasian families with at least one offspring affected by Hashimoto's thyroiditis (n=95) and Graves' disease (n=109) for two Fas gene polymorphisms (g-670 G-->A in the promoter region, g-154 C-->T in exon 7). METHODS: Extended transmission disequilibrium and chi(2) testing were performed. RESULTS: Neither polymorphism alone (P=0.44 and P=0.70) nor the promoter/exon 7 haplotypes (P=0.86) were associated with Hashimoto's thyroiditis. No association with Graves' disease was observed for the promoter polymorphism (P=0.91) and exon 7 (P=0.65) or the promoter/exon 7 haplotypes (P=0.80). CONCLUSION: In summary, our data do not suggest any significant contribution of common genetic Fas variants to the genetic risk of developing Hashimoto's thyroiditis or Graves' disease.

scholarly journals Immunoglobulin Gκ Antithyroid Peroxidase Antibodies in Hashimoto’s Thyroiditis: Epitope-Mapping Analysis1

1997 ◽  
Vol 82 (8) ◽  
pp. 2639-2644 ◽  
Author(s):  
Barbara Czarnocka ◽  
Marek Janota-Bzowski ◽  
Richard S. McIntosh ◽  
M. Suhail Asghar ◽  
Philip F. Watson ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Autoimmune Thyroid Disease ◽  
Epitope Mapping ◽  
Mapping Method ◽  
Hashimoto's Thyroiditis ◽  
Thyroid Peroxidase ◽  
Graves Disease ◽  
Autoimmune Thyroid ◽  
Immunodominant Region ◽  
High Affinity

Patients with autoimmune thyroid disease frequently have high affinity antibodies to thyroid peroxidase (TPO), although the role they play in disease pathogenesis is not known. We have previously prepared 37 monoclonal anti-TPO IgGκ Fab fragments from two patients with Hashimoto’s thyroiditis and demonstrated the similarity of these Fab sequences to those published previously, mainly derived from patients with Graves’ disease. In this paper, we describe epitope mapping of these Fabs using a previously characterized panel of murine monoclonal antibody (mAb) and show that the Fabs bind to two neighboring epitopes on native TPO. Although the epitope-mapping method differs from that used to characterize previously published TPO-reactive Fab sequences, it indicates a similarly restricted response to neighboring epitopes in both Graves’ disease and Hashimoto’s thyroiditis. The epitope mapping included mAb 47, which binds to a linear TPO peptide of known sequence in addition to native TPO. Although TPO-reactive Fab did not inhibit the binding of mAb 47, mAb 47 did inhibit the binding of Fab, indicating the likely site of the immunodominant region on native TPO. These results confirm the restricted nature of TPO antibody and further delineate the immunodominant region of native TPO as defined by the mAb.

scholarly journals Defect of a subpopulation of natural killer immune cells in Graves’ disease and Hashimoto’s thyroiditis: normalizing effect of dehydroepiandrosterone sulfate

2005 ◽  
Vol 152 (5) ◽  
pp. 703-712 ◽  
Author(s):  
Sebastiano Bruno Solerte ◽  
Sara Precerutti ◽  
Carmine Gazzaruso ◽  
Eleonora Locatelli ◽  
Mauro Zamboni ◽  
...  
Keyword(s):  
Nk Cells ◽  
Hashimoto’S Thyroiditis ◽  
Nk Cell ◽  
Secretory Activity ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Tnf Α

Background: The study of the natural killer (NK) immune compartment could provide important findings to help in the understanding of some of the pathogenetic mechanisms related to autoimmune thyroid diseases (Graves’ disease (GD) and Hashimoto’s thyroiditis (HT)). Within this context, it was suggested that alterations in NK cell cytotoxicity (NKCC) and NK production of cytokines might occur in subjects with GD and HT, whereas the normalization of NK functions could potentially contribute to the prevention of the onset or the progression of both diseases. Objective: Due to the hypothesis of alterations in NK in autoimmune thyroid diseases, we were interested to evaluate NKCC in GD and HT patients and to modulate NK function and secretory activity with cytokines and dehydroepiandrosterone sulfate (DHEAS) in an attempt to normalize NK cell defect. Design: We studied 13 patients with recent onset Graves’ disease, 11 patients with Hashimoto’s thyroiditis at first diagnosis and 15 age-matched healthy subjects. Methods: NK cells were concentrated at a density of 7.75 × 106 cells/ml by negative immunomagnetic cell separation and validated by FACScan as CD16 + /CD56 + cells. NK cells were incubated with interleukin-2 (IL-2) and interferon-β (IFN-β) and co-incubated with DHEAS at different molar concentrations for measuring NKCC and the secretory pattern of tumor necrosis factor-α (TNF-α) from NK cells. Results: Lower spontaneous, IL-2- and IFN-β-modulated NKCC was demonstrated in GD and HT patients compared with healthy subjects (P < 0.001). A decrease in spontaneous and IL-2-modulated TNF-α release from NK cells was also found in both groups of patients (P < 0.001). The co-incubation of NK cells with IL-2/IFN-β + DHEAS at different molar concentrations (from 10−8 to 10−5 M/ml/NK cells) promptly normalized NKCC and TNF-α secretion in GD and HT patients. Conclusions: A functional defect of a subpopulation of NK immune cells, involving both NKCC and the secretory activity, was demonstrated in newly-diagnosed GD and HT patients. This defect can be reversed by a dose-dependent treatment with DHEAS. The impairment of NK cell activity in autoimmune thyroid diseases could potentially determine a critical expansion of T/B-cell immune compartments leading to the generation of autoantibodies and to the pathogenesis of thyroid autoimmunity.

scholarly journals Polymorphisms of IKZF3 Gene and Autoimmune Thyroid Diseases: Associated with Graves’ Disease but Not with Hashimoto’s Thyroiditis

2018 ◽  
Vol 45 (5) ◽  
pp. 1787-1796 ◽  
Author(s):  
Ling Li ◽  
Xiaolian Ding ◽  
Xuan Wang ◽  
Qiuming Yao ◽  
Xiaoqing Shao ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Zinc Finger Protein ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Control Group ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Significant Difference ◽  
Proliferation And Differentiation

Background/Aims: The IKZF3 gene encodes a zinc-finger protein that plays an important role in the proliferation and differentiation of B lymphocytes. Autoimmune thyroid diseases (AITDs), mainly include Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are probably caused by the aberrant proliferation of B cells. The objective of this study was to explore the association between IKZF3 polymorphisms and AITDs. Methods: We examined 915 AITD patients (604 GD and 311 HT) and 814 healthy controls. IKZF3 variants (rs2941522, rs907091, rs1453559, rs12150079 and rs2872507) were tested by PCR-ligase detection reaction. Results: It was manifested that that the minor alleles of the five loci increased susceptibility to GD (p<0.05 for rs2941522, and p<0.01 for rs907091, rs1453559, rs12150079 and rs2872507) but in HT patients, these loci showed no significant difference compared with controls. Similarly, the genotype distributions of GD patients manifested obvious differences in all these loci compared with the control group, whereas no statistical differences were observed between HT patients and controls. Furthermore, bioinformatics tools were used to analyze rs1453559, rs12150079 and rs907091. These variants were believed to be the transcription regulator. Conclusion: It is the first time we reported the association between the IKZF3 polymorphisms and GD, indicating that IKZF3 gene tends to bean important risk factor for the development of GD.

scholarly journals IRF7 Gene Variations Confer Susceptibility to Autoimmune Thyroid Diseases and Graves’ Ophthalmopathy

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Qiuming Yao ◽  
Xiaofei An ◽  
Jing Zhang ◽  
Kaida Mu ◽  
Ling Li ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Susceptibility Gene ◽  
Thyroid Diseases ◽  
Minor Allele ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Graves Ophthalmopathy ◽  
Significant Difference

The objective of this study was to investigate whether IRF7 polymorphisms are associated with autoimmune thyroid diseases (AITDs). We selected three single nucleotide polymorphisms (SNPs) of IRF7, namely, rs1061501, rs1131665, and rs1061502 for genotyping using PCR-based ligase detection reaction (LDR) method in a total of 1659 participants (592 with Graves’ disease, 297 with Hashimoto’s thyroiditis, and 770 healthy controls). Gene-disease and genotype-clinical phenotype associations were evaluated for the three SNPs. Our results showed that the AG genotype and the minor allele G frequency of rs1131665 and rs1061502 in AITD patients were both higher than those of the controls (rs1131665: AG genotype: P=0.017, OR=1.968; allele G: P=0.018, OR=1.946; rs1061502: AG genotype: P=0.029, OR=1.866; allele G: P=0.031, OR=1.847). Subgroup analysis also showed that the AG genotype and the minor allele G frequency of rs1131665 and rs1061502 in Graves’ disease patients were both higher than those of the controls (rs1131665: AG genotype: P=0.015, OR=2.074; allele G: P=0.016, OR=2.048; rs1061502: AG genotype: P=0.034, OR=1.919; allele G: P=0.035, OR=1.898). Furthermore, the allele G frequency of rs1061501 was associated with Graves’ ophthalmopathy (P=0.035, OR=1.396). No significant difference in IRF7 polymorphisms was found between Hashimoto’s thyroiditis patients and controls. Our study has revealed for the first time that IRF7 is a susceptibility gene for AITD, especially for Graves’ disease and Graves’ ophthalmopathy.

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