Association of the polymorphisms of chemokine genes (<i>IL8, RANTES, MIG, IP10, MCP1 and IL16</i>) with the pathogenesis of autoimmune thyroid diseases

Akahane, Maiko; Watanabe, Mikio; Inoue, Naohisa; Miyahara, Yumi; Arakawa, Yuya; Inoue, Yumi; Katsumata, Yuka; Hidaka, Yoh; Iwatani, Yoshinori

doi:10.3109/08916934.2015.1134507

Cited by 24 publications

(21 citation statements)

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“…CXCL8 (IL-8), a chemoattractant for lymphocytes, was found at higher levels in TFCs from patients with Graves' disease (GD) [24]. Polymorphisms of MCP1, ICAM1 and IL8 have also been reported to have possible associations with the pathogenesis of AITD [25]. Our research confirmed the expression of these genes and suggested the possibility for transcriptional regulation from an epigenetic perspective.…”

Section: Discussionsupporting

confidence: 76%

Changes in histone H3 lysine 4 trimethylation in Hashimoto’s thyroiditis

Sun

Liu

et al. 2019

Arch Med Sci

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Introduction: The precise pathogenesis of Hashimoto's thyroiditis (HT) is yet to be fully elucidated. The role of epigenetics in the pathogenesis of HT has scarcely been addressed. Tri-methylated histone H3 lysine 4 (H3K4me3) is generally regarded as a marker of gene activation. The aim of this study was to explore genome-wide H3K4me3 patterns and global protein levels in primary thyrocytes and thyroids from HT patients. Material and methods: Chromatin immunoprecipitation sequencing (ChIP-seq) was used to analyze genome-wide H3K4me3 patterns in primary cultured thyrocytes from three HT females and three age-matched female control subjects. Western blotting was used to analyze global H3K4me3 levels in thyrocytes and thyroid tissues. Gene expression was determined using RT-PCR. Mixed-lineage leukemia 1 (MLL1) protein levels were measured by western blotting and immunohistochemistry. Results: Nine genes-TG, CXCL8, CCL2, CXCL10, FASLG, ICAM1, ITGA4, IL18 and TRAIL-showed increased H3K4me3 enrichment in promoter regions around the transcriptional start sites, and gene expression of ICAM1, CCL2 and CXCL8 was consistently increased (p < 0.05). KEGG pathway analysis suggested that differential peak-related genes were markedly associated with autoimmune thyroid disease< 0.05). Conclusions: This first investigation of genome-wide H3K4me3 distribution in thyroid follicular cells suggested that genes associated with autoimmune thyroiditis showed differential H3K4me3 enrichment, which was partly related to gene expression. Global H3K4me3 changes and increased MLL1 expression were found in thyroid tissues from HT patients.

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Section: Discussionsupporting

confidence: 76%

Changes in histone H3 lysine 4 trimethylation in Hashimoto’s thyroiditis

Sun

Liu

et al. 2019

Arch Med Sci

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“…28,31 Despite former reports indicating that the CCL5 variant, rs2107538, might be associated with other autoimmune endocrine conditions, our study failed to demonstrate its association with AAD. 21,22 A unique analysis in an Italian AAD cohort concerned the RANTES receptor gene (CCR5)-its variant characterized by a 32 -base pair deletion within the coding region did not appear associated with adrenal autoimmunity. 32 However, both AAD cohorts, Italian and ours, were relatively small and hence underpowered to detect a minor effect.…”

Section: Methodsmentioning

confidence: 99%

“…21 Likewise, the promoter variant rs2107538 (G -403A) appeared less frequent in patients with autoimmune thyroid disease, although the sample size was modest in that study. 22 There have been no reports on CCL5 polymorphisms in AAD to date. This study was therefore designed to evaluate the likely implication of RANTES in primary autoimmune adrenal failure, by investigation of rs2107538, the most commonly reported functional CCL5 variant, and assessment of serum levels of this chemokine in affected subjects.…”

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confidence: 99%

Elevated serum RANTES chemokine in autoimmune Addison’s disease

Fichna¹,

Żurawek²,

Budny³

et al. 2018

Polish Archives of Internal Medicine

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INTRODUCTION Regulated on activation, normal T‑cell expressed and secreted chemokine (RANTES), the product of the CCL5 gene, is involved in trafficking immune cells into the inflammation site. It acts as coactivator of T cells and promotes polarization of the immune response towards the Th1 profile. In autoimmune Addison disease (AAD), the adrenal cortex is gradually destroyed by adrenal‑specific immune cell infiltration. RANTES might be implicated in autoimmune adrenal failure through recruitment and activation of the immune cells. Furthermore, the promoter CCL5 variant, rs2107538, seems to be associated with autoimmune endocrine conditions: diabetes and thyroid disease. OBJECTIVES Our analysis was designed to evaluate the prevalence of rs2107538 and serum RANTES levels in AAD. PATIENTS AND METHODS rs2107538 was genotyped using TaqMan technology in 239 individuals with AAD and 542 controls, while serum RANTES levels were evaluated by an enzyme‑linked immunosorbent assay in 114 patients with AAD and 111 healthy age- and sex‑matched individuals. RESULTS No differences were found in rs2107538 genotype or allele frequencies between patients and controls (P = 0.53 and P = 0.39, respectively), and no association was detected with age at AAD onset (P = 0.14). Serum RANTES levels were elevated in patients with AAD compared with controls (mean [SD], 59.2 [30.3] ng/ml vs 45.5 [20.4] ng/ml, P = 0.001). Healthy carriers of various rs2107538 genotypes demonstrated differences in serum RANTES levels (P = 0.02), whereas AAD patients did not (P = 0.26). No correlation was found between circulating RANTES levels and age, AAD duration, serum autoantibodies, hydrocortisone dose, and body mass (P >0.05). CONCLUSIONS This study demonstrates for the first time elevated serum RANTES levels in AAD and confirms that rs2107538 may affect serum chemokine levels.

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“…Most recently, a single nucleotide polymorphism (SNP) (rs2276886) within the CXCL9 (MIG) gene was newly identified to be associated with HT susceptibility in Japanese populations (Akahane et al, 2016). Chemokines such as CXCL9 are a class of cytokine proteins that act as signaling molecules, regulating immune and inflammatory responses and modulating cell migration properties and localization of target cells such as leucocytes (Moser et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…The polymorphisms of genes, including chemokines, have been conclusively identified as risk factors in the pathogenesis of HT (Akahane et al, 2016). A relationship between polymorphisms of CXCL9 and HT in the Japanese population has been shown (Akahane et al, 2016). However, the contributions of CXCL9 to the etiology and pathogenesis of HT have not yet been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

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

Mo¹,

Li²,

Peng³

et al. 2019

Genetic Testing and Molecular Biomarkers

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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.

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Association of the polymorphisms of chemokine genes (IL8, RANTES, MIG, IP10, MCP1 and IL16) with the pathogenesis of autoimmune thyroid diseases

Cited by 24 publications

References 55 publications

Changes in histone H3 lysine 4 trimethylation in Hashimoto’s thyroiditis

Changes in histone H3 lysine 4 trimethylation in Hashimoto’s thyroiditis

Elevated serum RANTES chemokine in autoimmune Addison’s disease

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

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