Association of <i>TXNDC5</i>
 gene polymorphisms and susceptibility to nonsegmental vitiligo in the Korean population

Jeong, Ki‐Heon; Shin, Min Kyung; Uhm, Yoon Kyung; Kim, H. J.; Chung, Joo‐Ho; Lee, M. H.

doi:10.1111/j.1365-2133.2009.09574.x

Cited by 17 publications

(15 citation statements)

References 33 publications

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“…TXNDC5 expression is induced by hypoxia (Sullivan et al., 2003), and variants in this gene have been associated with a number of autoimmune diseases, including rheumatoid arthritis (Chang et al., 2011) and vitiligo (Jeong et al., 2010). As for HDAC9, variants in TXNDC5 have not previously been associated with immune cell infiltration, again suggesting that iQTLs can uncover clinically relevant associations.…”

Section: Resultsmentioning

confidence: 99%

Histopathological Image QTL Discovery of Immune Infiltration Variants

et al. 2018

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SUMMARY Genotype-to-phenotype association studies typically use macroscopic physiological measurements or molecular readouts as quantitative traits. There are comparatively few suitable quantitative traits available between cell and tissue length scales, a limitation that hinders our ability to identify variants affecting phenotype at many clinically informative levels. Here we show that quantitative image features, automatically extracted from histopathological imaging data, can be used for image quantitative trait loci (iQTLs) mapping and variant discovery. Using thyroid pathology images, clinical metadata, and genomics data from the Genotype-Tissue Expression (GTEx) project, we establish and validate a quantitative imaging biomarker for immune cell infiltration. A total of 100,215 variants were selected for iQTL profiling and tested for genotype-phenotype associations with our quantitative imaging biomarker. Significant associations were found in HDAC9 and TXNDC5. We validated the TXNDC5 association using GTEx cis-expression QTL data and an independent hypothyroidism dataset from the Electronic Medical Records and Genomics network.

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Section: Resultsmentioning

confidence: 99%

Histopathological Image QTL Discovery of Immune Infiltration Variants

et al. 2018

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“…They genotyped seven SNPs and found that three exonic SNPs (rs1043784, rs7764128 and rs8643) were statistically associated with NSV. The haplotypes AGG and GAA, consisting of rs1043784, rs7764128 and rs8643, demonstrated a significant association with NSV [18]. Lin et al reported that SNP rs13873 and haplotypes rs1225934 to rs13873 of BMP6-TXNDC5 genes were significantly associated with schizophrenia [19].…”

Section: Discussionmentioning

confidence: 99%

Investigating a pathogenic role for TXNDC5 in rheumatoid arthritis

et al. 2011

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IntroductionExpression of TXNDC5, which is induced by hypoxia, stimulates cell proliferation and angiogenesis. Our previous study detected increased TXNDC5 expression in the synovial tissues of rheumatoid arthritis (RA) patients using proteomic methods. The current study investigated a pathogenic role for TXNDC5 in RA.MethodExpression of TXNDC5 in synovial membranes was quantitatively analyzed by immunohistochemistry, Western blotting and real-time polymerase chain reaction (PCR). Serum TXNDC5 levels and serum anti-TXNDC5 antibody levels were determined using sandwich enzyme-linked immunosorbent assay (ELISA). A total of 96 single nucleotide polymorphisms (SNPs) in or near the TXNDC5 gene were genotyped using custom-designed Illumina 96-SNP VeraCode microassay. Allele frequencies and genotype frequencies of SNPs were assessed using a case-control design in a cohort of 267 Chinese patients with RA, 51 patients with ankylosing spondylitis (AS) and 160 healthy controls. Additional genotyping of 951 patients with RA and 898 healthy controls was performed for four SNPs (rs2277105, rs369086, rs443861 and rs11962800) using the TaqMan method.ResultsReal-time PCR, Western blotting and immunohistochemistry detected significantly higher TXNDC5 expression in the synovial tissues of RA patients compared to samples from patients with osteoarthritis (OA) or AS. ELISA detected significantly higher levels of TXNDC5 in the blood of RA patients compared to OA, AS and systemic lupus erythematosus patients, and healthy controls. ELISA did not detect significantly different levels of anti-TXNDC5 antibody in the blood of RA, OA and AS patients and healthy controls. A total of 9 SNPs (rs9505298, rs41302895, rs1225936, rs1225938, rs372578, rs443861, rs408014, rs9392189 and rs2743992) showed significant association with RA, while 16 SNPs (rs1044104, rs1225937, rs1225938, rs372578, rs89715, rs378963, rs1225944, rs1225947, rs1238994, rs369086, rs408014, rs368074, rs1225954, rs1225955, rs13209404 and rs3812162) showed significant association with AS. Taqman SNP assay demonstrated that rs443861 has an association with RA, which correlates with the microassay results.ConclusionsTXNDC5 is up-regulated in synovial tissues of RA patients. TXNDC5 has a genetic effect on the risk of RA and AS.

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“…investigated the role of TXNDC5 in development of the skin disorder vitiligo [61]. A total of 230 Korean patients with non-segmental vitiligo were investigated for SNPs in the TXNDC5 gene; in total, seven SNPs were identified in the TXNDC5 gene, three of which (rs1043784, rs7764128, and rs8643) demonstrated an association with the vitiligo phenotype [61]. Although relevant in vivo studies have been conducted on the role of TXNDC5 no biochemical parameters have been evaluated, with regard to its role in disulfide bond oxidation and reduction.…”

Section: The Human Pdi Gene Familymentioning

confidence: 99%

The human protein disulfide isomerase gene family

2012

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Enzyme-mediated disulfide bond formation is a highly conserved process affecting over one-third of all eukaryotic proteins. The enzymes primarily responsible for facilitating thiol-disulfide exchange are members of an expanding family of proteins known as protein disulfide isomerases (PDIs). These proteins are part of a larger superfamily of proteins known as the thioredoxin protein family (TRX). As members of the PDI family of proteins, all proteins contain a TRX-like structural domain and are predominantly expressed in the endoplasmic reticulum. Subcellular localization and the presence of a TRX domain, however, comprise the short list of distinguishing features required for gene family classification. To date, the PDI gene family contains 21 members, varying in domain composition, molecular weight, tissue expression, and cellular processing. Given their vital role in protein-folding, loss of PDI activity has been associated with the pathogenesis of numerous disease states, most commonly related to the unfolded protein response (UPR). Over the past decade, UPR has become a very attractive therapeutic target for multiple pathologies including Alzheimer disease, Parkinson disease, alcoholic and non-alcoholic liver disease, and type-2 diabetes. Understanding the mechanisms of protein-folding, specifically thiol-disulfide exchange, may lead to development of a novel class of therapeutics that would help alleviate a wide range of diseases by targeting the UPR.

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Association of TXNDC5 gene polymorphisms and susceptibility to nonsegmental vitiligo in the Korean population

Abstract: These results suggest that TXNDC5 gene polymorphisms are associated with the development of NSV in the Korean population.

Cited by 17 publications

References 33 publications

Histopathological Image QTL Discovery of Immune Infiltration Variants

Histopathological Image QTL Discovery of Immune Infiltration Variants

Investigating a pathogenic role for TXNDC5 in rheumatoid arthritis

The human protein disulfide isomerase gene family

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