Associations of lymphotoxin-a (LTA) rs909253 A/G gene polymorphism, plasma level and risk of ankylosing spondylitis in a Chinese Han population

Zhu, Aiping; Yang, Zhicheng; Zhang, Hui; Liu, Ruiping

doi:10.1038/s41598-020-57927-6

Cited by 3 publications

(4 citation statements)

References 26 publications

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“…However, the absence of LTA or its receptor LTβR signi cantly impacts the development of lymphoid organs [52], while maintaining effective lymphoid tissue structure may aid in appropriate immune surveillance and in ammation regulation. In autoimmune diseases like ankylosing spondylitis, patients have been found to exhibit lower levels of plasma LTA [53]. On the other hand, activation of LTβR on the surface of stromal cells leads to the production of chemokines and cell adhesion molecules [49].…”

Section: Discussionmentioning

confidence: 99%

Protein Level Ratios as Causal Factors in Primary Sclerosing Cholangitis: Insights from a Two-Sample Mendelian Randomization Study

Zhou,

Xu,

Wang

et al. 2024

Preprint

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Background Primary Sclerosing Cholangitis (PSC) currently lacks effective biomarkers and therapeutic targets. The study of protein level ratios may offer new insights for addressing this challenge. Methods The summary statistics for PSC in this study was sourced from the International PSC Study Group, encompassing 2,871 PSC patients and 12,019 control participants. Protein quantitative trait loci data were sourced from the Olink proteomics platform, facilitating the identification of 2,821 significant protein level ratios. Furthermore, we conducted a Mendelian Randomization analysis to explore the causal relationship between the two factors, applying a stringent Bonferroni correction threshold of 1.77E-5. The primary analytical method employed was the Inverse Variance Weighted (IVW) approach, which was further reinforced by comprehensive heterogeneity analyses, horizontal pleiotropy testing, outlier detection, and “leave-one-out” sensitivity analysis. Results We identified a positive causal association between the protein level ratios of Low-Density Lipoprotein Receptor-Related Protein 11/ Nectin Cell Adhesion Molecule 2 (IVW odds ratio (OR): 1.84; 95% confidence interval (CI): 1.40–2.41, P = 1.07E-05) and Tumor Necrosis Factor Receptor Superfamily Member 13B/ Tumor Necrosis Factor Receptor Superfamily Member 9 (IVW OR: 2.72, 95% CI: 1.77–4.19, P = 5.56E-06) and the risk of PSC. Conversely, the protein level ratios of Lymphotoxin Alpha/ Lymphotoxin Beta Receptor (IVW OR: 0.50, 95% CI: 0.43–0.58, P = 7.58E-20) and Nectin Cell Adhesion Molecule 2/ Tumor Necrosis Factor Receptor Superfamily Member 14 (IVW OR: 0.55, 95% CI: 0.44–0.69, P = 2.17E-07) were found to have an inverse causal relationship with the risk of PSC. Significantly, all analyses demonstrated a lack of horizontal pleiotropy and heterogeneity. Conclusion These results identify potential new biomarkers for PSC diagnosis and suggest targets for treatment, laying the groundwork for future drug development.

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Section: Discussionmentioning

confidence: 99%

Protein Level Ratios as Causal Factors in Primary Sclerosing Cholangitis: Insights from a Two-Sample Mendelian Randomization Study

Zhou,

Xu,

Wang

et al. 2024

Preprint

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“…Genome-wide association research has shown an abundance of additional loci ( 13 ), including ERAP1 and interleukin-23 receptor (IL-23R). HLA-B27 poses the highest risk and is identified in 90% of AS patients.…”

Section: The Role Of Hla-b27 In Asmentioning

confidence: 99%

Vesicular traffic-mediated cell-to-cell signaling at the immune synapse in Ankylosing Spondylitis

et al. 2023

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The chronic inflammatory disease ankylosing spondylitis (AS) is marked by back discomfort, spinal ankylosis, and extra-articular symptoms. In AS, inflammation is responsible for both pain and spinal ankylosis. However, the processes that sustain chronic inflammation remain unknown. Despite the years of research conducted to decipher the intricacy of AS, little progress has been made in identifying the signaling events that lead to the development of this disease. T cells, an immune cell type that initiates and regulates the body’s response to infection, have been established to substantially impact the development of AS. T lymphocytes are regarded as a crucial part of adaptive immunity for the control of the immune system. A highly coordinated interaction involving antigen-presenting cells (APCs) and T cells that regulate T cell activation constitutes an immunological synapse (IS). This first phase leads to the controlled trafficking of receptors and signaling mediators involved in folding endosomes to the cellular interface, which allows the transfer of information from T cells to APCs through IS formation. Discrimination of self and nonself antigen is somatically learned in adaptive immunity. In an autoimmune condition such as AS, there is a disturbance of self/nonself antigen discrimination; available findings imply that the IS plays a preeminent role in the adaptive immune response. In this paper, we provide insights into the genesis of AS by evaluating recent developments in the function of vesicular trafficking in IS formation and the targeted release of exosomes enriched microRNAs (miRNA) at the synaptic region in T cells.

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“…It can help communicate lymphocytes and stromal cells and subsequently induce cancer cells cytotoxicity. 8,11,12 LTA has been implicated in the pathogenesis of acute and chronic HCV infection. [13][14][15] As an important mediator of hepatic fibrogenesis, TNF-β is released by lymphocytes (T cells, B cells, and natural killer cells) as an inflammatory response in chronic HCV patients.…”

Section: Introductionmentioning

confidence: 99%

“…16,17 Several studies examined the role of LT-α polymorphism in different immune-mediated diseases and it has been associated with diseases such as rheumatoid arthritis, 18 systemic lupus erythematosus, 19 cardiac diseases, 20,21 and ankylosing spondylitis. 12 Several polymorphisms of the LT-α gene were identified and Messer first reported the existence of a single nucleotide polymorphism (SNP) in the intron of LT-α at position 252 (G>A, designated rs909253, which is associated with overexpression of LT-α. 22 As lymphotoxin α is an important mediator of hepatic fibrogenesis, it may be helpful to elucidate the contribution of LTA gene polymorphism in different stages of CHC infection.…”

Section: Introductionmentioning

confidence: 99%

Role of Lymphotoxin-α Gene Polymorphism in Hepatitis C Virus-Related Chronic Liver Disorders

Galal¹,

Tammam²,

Aal³

et al. 2021

IDR

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Background: Tumor necrosis factor (TNF) family includes lymphotoxin-alpha (LTA) which is a pro-inflammatory cytokine which plays a role in hepatic fibrogenesis. LTA gene polymorphism plays a role in different inflammatory and immunomodulatory diseases. This polymorphism is also suggested to affect chronic hepatitis C (CHC) infection course. Aim: To study the contribution of LTA gene polymorphism in different chronic hepatitis C stages and hepatocellular carcinoma risk. Patients and Methods: Our study included 108 chronic HCV patients grouped according to the disease stage. Group (A): CHC, group (B): liver cirrhosis (LC), group (C): LC with HCC, and group (D): healthy controls. Routine laboratory investigations, polymerase chain reaction (PCR) for quantification of HCV, abdominal ultrasonography, and Liver stiffness measurement (LSM) were done. Child-Turcotte-Pugh, Model for end-stage liver disease (MELD), and Fibrosis index based on 4 (FIB-4) scores were calculated. We used the PCRrestriction fragment length polymorphism technique for lymphotoxin-α genotyping. Results: The A/G genotype was predominant in all groups. In HCC patients, G/G genotype was more frequent (31.8%) than in the LC group (19.4%), CHC group (17.8%), and controls (4.17%). A significant association was found between LTA genotypes and the child classes in HCC (P<0.01) but not in LC patients (P>0.05). HCC patients carrying A/G genotype had higher MELD scores than other genotypes. Multivariate binary logistic regression analysis confirmed that LTA G/G genotype and low platelet count were independent predictors for HCC development in patients with HCV-related LC. Conclusion: Detection of LTA G/G genotype in chronic HCV patients could help to recognize high-risk patients for disease progression and HCC development.

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Associations of lymphotoxin-a (LTA) rs909253 A/G gene polymorphism, plasma level and risk of ankylosing spondylitis in a Chinese Han population

Cited by 3 publications

References 26 publications

Protein Level Ratios as Causal Factors in Primary Sclerosing Cholangitis: Insights from a Two-Sample Mendelian Randomization Study

Protein Level Ratios as Causal Factors in Primary Sclerosing Cholangitis: Insights from a Two-Sample Mendelian Randomization Study

Vesicular traffic-mediated cell-to-cell signaling at the immune synapse in Ankylosing Spondylitis

Role of Lymphotoxin-α Gene Polymorphism in Hepatitis C Virus-Related Chronic Liver Disorders

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