Genetic risk and protective factors of TNFSF15 gene variants detected using single nucleotide polymorphisms in Hungarians with psoriasis and psoriatic arthritis

Képíró, László; Széll, Márta; Kovács, László; Keszthelyi, Péter; Kemény, Lajos; Gyulai, Rolland

doi:10.1016/j.humimm.2013.11.006

Cited by 24 publications

(22 citation statements)

References 23 publications

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“…Precisely, TL1A and DR3 expression is significantly increased, in an inflammation-specific manner, in both serum and inflamed tissues in IBD patients and in murine experimental ileitis ( 19 ). Genome-wide association studies have identified polymorphisms associated with IBD risk in the gene that encodes for TL1A protein ( 20 – 24 ). Finally, studies in animal models of intestinal inflammation have demonstrated that sustained expression of TL1A leads to chronic small-intestinal inflammation, whereas blockade of the TL1A/DR3 axis suppresses murine colitis ( 7 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

Death Receptor 3 Signaling Controls the Balance between Regulatory and Effector Lymphocytes in SAMP1/YitFc Mice with Crohn’s Disease-Like Ileitis

Buttó

Buela

et al. 2018

Front. Immunol.

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Death receptor 3 (DR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, has been implicated in regulating T-helper type-1 (TH1), type-2 (TH2), and type-17 (TH17) responses as well as regulatory T cell (Treg) and innate lymphoid cell (ILC) functions during immune-mediated diseases. However, the role of DR3 in controlling lymphocyte functions in inflammatory bowel disease (IBD) is not fully understood. Recent studies have shown that activation of DR3 signaling modulates Treg expansion suggesting that stimulation of DR3 represents a potential therapeutic target in human inflammatory diseases, including Crohn’s disease (CD). In this study, we tested a specific DR3 agonistic antibody (4C12) in SAMP1/YitFc (SAMP) mice with CD-like ileitis. Interestingly, treatment with 4C12 prior to disease manifestation markedly worsened the severity of ileitis in SAMP mice despite an increase in FoxP3+ lymphocytes in mesenteric lymph node (MLN) and small-intestinal lamina propria (LP) cells. Disease exacerbation was dominated by overproduction of both TH1 and TH2 cytokines and associated with expansion of dysfunctional CD25−FoxP3+ and ILC group 1 (ILC1) cells. These effects were accompanied by a reduction in CD25+FoxP3+ and ILC group 3 (ILC3) cells. By comparison, genetic deletion of DR3 effectively reversed the inflammatory phenotype in SAMP mice by promoting the expansion of CD25+FoxP3+ over CD25−FoxP3+ cells and the production of IL-10 protein. Collectively, our data demonstrate that DR3 signaling modulates a multicellular network, encompassing Tregs, T effectors, and ILCs, governing disease development and progression in SAMP mice with CD-like ileitis. Manipulating DR3 signaling toward the restoration of the balance between protective and inflammatory lymphocytes may represent a novel and targeted therapeutic modality for patients with CD.

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Section: Introductionmentioning

confidence: 99%

Death Receptor 3 Signaling Controls the Balance between Regulatory and Effector Lymphocytes in SAMP1/YitFc Mice with Crohn’s Disease-Like Ileitis

Buttó

Buela

et al. 2018

Front. Immunol.

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“…VEGI maps to human chromosome 9q32 and contains 4 exons and 3 introns. VEGI gene polymorphisms have exhibited a connection with certain inflammatory and autoimmune diseases, such as Crohn's Disease ( 18 ), inflammatory bowel disease ( 19 ), and psoriatic arthritis ( 20 ). However, the association between VEGI gene polymorphisms and breast cancer in Chinese people has never been studied.…”

Section: Introductionmentioning

confidence: 99%

A case-control study about the association between vascular endothelial growth inhibitor gene polymorphisms and breast cancer risk in female patients in Northeast China

Han¹,

Liu²,

Xu³

et al. 2016

Chinese Journal of Cancer Research

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Objective The inhibition of the neovascularization in tumors is a potential therapeutic target of cancer. Vascular endothelial growth inhibitor (VEGI) is a member of the TNF superfamily which has the ability to suppress the formation of new vessels in tumors. In order to study the association between VEGI gene polymorphisms and breast cancer risk, a case-control study was conducted in Chinese Han women in Northeast China. Methods Our study involved 708 female breast cancer patients and 685 healthy volunteers. Four SNPs of VEGI gene were analyzed through the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The association between VEGI gene polymorphisms and breast cancer risk was analyzed in our study. The relation between VEGI gene variants and clinical features of breast cancer including lymph node (LN) metastasis, estrogen receptor (ER), progestrogen receptor (PR), tumor protein 53 (p53), human epidermal growth factor receptor 2 (Her-2) and triple negative (ER-/PR-/Her-2-) status was analyzed as well.Results We found that the CT genotype and T allele of rs6478106 were more frequent in patients than in controls. There was also a statistical difference in the distribution of Crs6478106Grs4263839 haplotype between patients and controls. In addition, SNP rs6478106 and rs4979462 were related with the Her-2 status. Conclusions Our results suggest that VEGI gene variants may be related to the breast cancer risk and the clinical features of breast cancer in Chinese Han women in Northeast China.

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“…TNFSF15 , encoding a member of the tumor necrosis factor superfamily of cytokines, is primarily expressed in endothelial cells and has previously been implicated in susceptibility to Crohn’s disease ( 28 ). Although a previous study found nominal association between variants in this locus and psoriasis susceptibility in a Hungarian population ( 29 ), we establish 9q32 as a genome-wide significant susceptibility locus for the first time here.…”

Section: Resultsmentioning

confidence: 41%

Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling

Dand

Mucha

Tsoi

et al. 2017

Human Molecular Genetics

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Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 × 10−8, OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency < 0.01) via gene-wide aggregation testing (IFIH1: pburden = 2.53 × 10−7, OR = 0.707; TYK2: pburden = 6.17 × 10−4, OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.

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Genetic risk and protective factors of TNFSF15 gene variants detected using single nucleotide polymorphisms in Hungarians with psoriasis and psoriatic arthritis

Cited by 24 publications

References 23 publications

Death Receptor 3 Signaling Controls the Balance between Regulatory and Effector Lymphocytes in SAMP1/YitFc Mice with Crohn’s Disease-Like Ileitis

Death Receptor 3 Signaling Controls the Balance between Regulatory and Effector Lymphocytes in SAMP1/YitFc Mice with Crohn’s Disease-Like Ileitis

A case-control study about the association between vascular endothelial growth inhibitor gene polymorphisms and breast cancer risk in female patients in Northeast China

Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling

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