Dataset Information

Microarray Data of Lacrimal Gland Implicates Dysregulated Protein Processing in Endoplasmic Reticulum in Graves' Ophthalmopathy.

ABSTRACT: Graves' ophthalmopathy (GO) has become one of the most common orbital diseases. Although some evidences announced the potential mechanism of pathological changes in extraocular muscle and orbital adipose tissue, little is known about that in lacrimal enlargement of GO patients. Thus, gene expression profiles of lacrimal gland derived from GO patients and normal controls were investigated using the microarray datasets of GSE105149 and GSE58331. The raw data and annotation files of GSE105149 and GSE58331 were downloaded from Gene Expression Omnibus (GEO) database. Bioinformatics including differentially expressed genes (DEGs), Gene Ontology, Kyoto Encyclopedia of Gene and Genome (KEGG) pathway, protein-protein interaction (PPI) network construction, hub gene identification, and gene set variation analysis (GSVA) were successively performed. A total of 173 overlapping DEGs in GSE105149 and GSE58331 were screened out, including 20 up-regulated and 153 down-regulated genes. Gene Ontology, KEGG and GSVA analyses of these DEGs showed that the most significant mechanism was closely associated with endoplasmic reticulum (ER). Moreover, we identified 40 module genes and 13 hub genes which were also enriched in the ER-associated terms and pathways. Among the hub genes, five genes including HSP90AA1, HSP90B1, DNAJC10, HSPA5, and CANX may be involved in the dysfunction of protein processing in ER. Taken together, our observations revealed a dysregulated gene network which is essential for protein processing in ER in GO patients. These findings provided a potential mechanism in the progression of lacrimal enlargement in GO patients, as a new insight into GO pathogenesis.

SUBMITTER: Tu W

PROVIDER: S-EPMC7888479 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Microarray Data of Lacrimal Gland Implicates Dysregulated Protein Processing in Endoplasmic Reticulum in Graves' Ophthalmopathy.

Tu Wenling W Yao Jia J Mei Zhanjun Z Jiang Xue X Shi Yuhong Y

Frontiers in endocrinology 20210203

Graves' ophthalmopathy (GO) has become one of the most common orbital diseases. Although some evidences announced the potential mechanism of pathological changes in extraocular muscle and orbital adipose tissue, little is known about that in lacrimal enlargement of GO patients. Thus, gene expression profiles of lacrimal gland derived from GO patients and normal controls were investigated using the microarray datasets of GSE105149 and GSE58331. The raw data and annotation files of GSE105149 and G ...[more]

PMID: 33613444

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Project description:BackgroundA large gene region, called GD-1, was first described by this laboratory as linked to Graves' disease (GD) and included the gene for the thyroid-stimulating hormone receptor (TSHR). Recent studies have now suggested an association of TSHR intronic polymorphisms with GD. We have taken the opportunity to examine a population of well-characterized patients with autoimmune thyroid disease (AITD) typed for an additional thyroid susceptibility gene, the immunoregulatory gene for cytotoxic T-lymphocyte antigen 4 (CTLA-4), to examine its relationship with the susceptibility to GD endowed by TSHR gene polymorphisms.MethodsWe used TSHR-SNP-rs2268458, located in intron 1 of the TSHR gene, measured using standard PCR-RFLP procedures, as our marker for the TSHR gene association. We genotyped 200 patients with GD, 83 patients with Hashimoto's thyroiditis (HT), and 118 healthy controls (all female Caucasians).ResultsThe allele and genotype frequencies from GD patients, but not HT patients, were significantly different from controls. The frequency of the combined genotype (allele) CC + TC was significantly higher in GD patients versus controls, suggesting that the C-containing genotype increased the risk for GD in a dominant manner (p = 0.018, odds ratio [OR] = 1.8). When compared with CTLA-4 (A/G)(49) single-nucleotide polymorphism (SNP), we were unable to demonstrate additive risk in patients with established AITD. Further, subsetting the patients (n = 120) into those with clinically significant Graves' ophthalmopathy (GO) showed no association with the TSHR SNP.ConclusionsThese results demonstrated that the intronic TSHR-SNP-rs2268458 was associated with GD, but not with HT, thus indicating that the TSHR gene has the potential to increase susceptibility to GD. However, we were not able to demonstrate any additive risk with the CTLA-4 (A/G)(49) SNP, which is, therefore, an independent risk factor for AITD. This suggested that, within the limits of the study population, each of these two genes provided a small contribution to GD susceptibility and that neither was essential. In addition, there was no evidence for the TSHR gene association adding to the risk of developing GO. Direct functional analyses are now needed to help explain the mechanisms of this TSHR gene susceptibility to GD.

Dataset Information

Microarray Data of Lacrimal Gland Implicates Dysregulated Protein Processing in Endoplasmic Reticulum in Graves' Ophthalmopathy.

Publications

Microarray Data of Lacrimal Gland Implicates Dysregulated Protein Processing in Endoplasmic Reticulum in Graves' Ophthalmopathy.

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