Confirmation of TNIP1 and IL23A as susceptibility loci for psoriatic arthritis

Bowes, John; Orozco, Gisela; Flynn, Edward; Ho, Pauline; Brier, Rasha; Marzo‐Ortega, Helena; Coates, Laura C.; McManus, Ross; Ryan, Anthony W.; Kane, David; Korendowych, Eleanor; McHugh, Neil; FitzGerald, Oliver; Packham, Jon; Morgan, Ann W; Bruce, Ian N.; Barton, Anne

doi:10.1136/ard.2011.150102

Cited by 112 publications

(79 citation statements)

References 23 publications

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“…54 In addition, 347 ancestral-informative markers spanning the genome were genotyped. After application of quality controls by excluding samples that exhibited low call rates (,90%) and extreme heterozygosity (.5 SDs from the mean), revealed discrepancies between reported sex and genetic data, or were determined to be a duplicate or cryptic related to another sample (the proportion of alleles shared identical by descent .0.4), and after removing extreme population outliers based on global ancestry estimation and principal component analysis (calculated using the ancestral-informative markers in the ADMIXMAP 55,56 and EIGENSTRAT 57 programs, respectively), as described in other Large Lupus Association Study 2 reports, 58,59 a final data set of 15,864 unrelated patients was obtained (Table 2).…”

Section: Genotyping and Quality Controlmentioning

confidence: 99%

ABIN1 Dysfunction as a Genetic Basis for Lupus Nephritis

Caster¹,

Korte²,

Nanda

et al. 2013

Journal of the American Society of Nephrology

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The genetic factors underlying the pathogenesis of lupus nephritis associated with systemic lupus erythematosus are largely unknown, although animal studies indicate that nuclear factor (NF)-kB is involved. We reported previously that a knockin mouse expressing an inactive form of ABIN1 (ABIN1[D485N]) develops lupus-like autoimmune disease and demonstrates enhanced activation of NF-kB and mitogen-activated protein kinases in immune cells after toll-like receptor stimulation. In the current study, we show that ABIN1[D485N] mice develop progressive GN similar to class III and IV lupus nephritis in humans. To investigate the clinical relevance of ABIN1 dysfunction, we genotyped five single-nucleotide polymorphisms in the gene encoding ABIN1, TNIP1, in samples from European-American, African American, Asian, Gullah, and Hispanic participants in the Large Lupus Association Study 2. Comparing cases of systemic lupus erythematosus with nephritis and cases of systemic lupus erythematosus without nephritis revealed strong associations with lupus nephritis at rs7708392 in European Americans and rs4958881 in African Americans. Comparing cases of systemic lupus erythematosus with nephritis and healthy controls revealed a stronger association at rs7708392 in European Americans but not at rs4958881 in African Americans. Our data suggest that variants in the TNIP1 gene are associated with the risk for lupus nephritis and could be mechanistically involved in disease development via aberrant regulation of NF-kB and mitogen-activated protein kinase activity. 24: 174324: -175424: , 201324: . doi: 10.1681 Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by an abnormal immune response leading to autoantibody production, immune complex formation, T cell activation, and inflammatory cytokine release. 1 Multiple factors contribute to the immune response in SLE, including genetic, epigenetic, immunoregulatory, environmental, and hormonal factors. 1 Lupus nephritis (LN) occurs in about 50% of patients with SLE and is a major cause of morbidity and mortality. 2 The incidence of LN varies among different ethnic groups, suggesting that genetic factors play an important role in the pathogenesis. Patients with African ancestry are at Received February 11, 2013. Accepted May 7, 2013 D.J.C. and E.A.K. contributed equally to this work. J Am Soc NephrolPublished online ahead of print. Publication date available at www.jasn.org. LN,4 and that therapy is associated with undesirable short-and long-term adverse effects. Thus, identifying the molecular mechanisms responsible for the pathogenesis of LN is necessary to define more specific diagnostic and therapeutic targets. However, the complex interactions of genetic risks, environmental factors, and molecular events that contribute to the development of LN are only beginning to be defined. The transcription factor nuclear factor-kB (NF-kB) regulates the expression of hundreds of genes that control cell proliferation and survival, the cellular stress r...

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Section: Genotyping and Quality Controlmentioning

confidence: 99%

ABIN1 Dysfunction as a Genetic Basis for Lupus Nephritis

Caster¹,

Korte²,

Nanda

et al. 2013

Journal of the American Society of Nephrology

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“…In German and Chinese cohorts, the intronic rs2066808 IL-23A variant has been associated with psoriasis 125,126 , whereas in Northern Spaniards it has been associated with psoriatic arthritis 127 . Finally, these associations have been confirmed in a Romanian cohort 128 and a Caucasian cohort (British and Irish patients) 129 . Unfortunately, at present, no studies have evaluated the association of the IL-23A polymorphisms with the development of cardiovascular disease.…”

Section: Il-23a Genementioning

confidence: 61%

Innate Immunity in Coronary Disease. The Role of Interleukin-12 Cytokine Family in Atherosclerosis

Posadas-Sánchez

Vargas‐Alarcón

2018

RIC

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Atherosclerosis is a chronic, progressive, and multifactorial disease modulated by genetic and environmental factors. In recent years, the paradigm that explained atherosclerosis as resulting from a complex interaction between factors not accessible to medical intervention, and modifiable risk factors has changed. In this paradigm, alterations in lipid metabolism were the pivotal concept of atherosclerosis as a chronic degenerative disease. In the last years, an increasing number of observations have shown that the innate and adaptive immune responses to lipoprotein deposition and oxidation in the arterial wall significantly influence atherosclerosis. Currently, it is well recognized that the pathogenesis of atherosclerosis and its complications involves the inflammatory process, which includes the participation of several cytokines. Besides the classic cytokines involved in this process, the role of the interleukin-12 (IL-12) family has been recently demonstrated. This review describes our current understanding about the role of the family of IL-12 in atherosclerosis considering the participation of the genes that encode these cytokines in the genetic susceptibility to developing this disease.

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“…Naf1 is encoded by the TNIP1 gene, and single-nucleotide polymorphisms (SNPs) of TNIP that lead to a loss of control of NF-B activation have been reported to be associated with multiple inflammation-related autoimmune diseases (43,(45)(46)(47)(48)(49). Naf1 is ubiquitously expressed in human tissues and cell types, particularly in peripheral blood lymphocytes (17).…”

Section: Discussionmentioning

confidence: 99%

Naf1 Regulates HIV-1 Latency by Suppressing Viral Promoter-Driven Gene Expression in Primary CD4 ⁺ T Cells

Wang

Kuang

et al. 2017

J Virol

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HIV-1 latency is characterized by reversible silencing of viral transcription driven by the long terminal repeat (LTR) promoter of HIV-1. Cellular and viral factors regulating LTR activity contribute to HIV-1 latency, and certain repressive cellular factors modulate viral transcription silencing. Nef-associated factor 1 (Naf1) is a host nucleocytoplasmic shuttling protein that regulates multiple cellular signaling pathways and HIV-1 production. We recently reported that nuclear Naf1 promoted nuclear export of unspliced HIV-1 gag mRNA, leading to increased Gag production. Here we demonstrate new functions of Naf1 in regulating HIV-1 persistence. We found that Naf1 contributes to the maintenance of HIV-1 latency by inhibiting LTR-driven HIV-1 gene transcription in a nuclear factor kappa B-dependent manner. Interestingly, Naf1 knockdown significantly enhanced viral reactivation in both latently HIV-1-infected Jurkat T cells and primary central memory CD4+ T cells. Furthermore, Naf1 knockdown in resting CD4+ T cells from HIV-1-infected individuals treated with antiretroviral therapy significantly increased viral reactivation upon T-cell activation, suggesting an important role of Naf1 in modulating HIV-1 latency in vivo. Our findings provide new insights for a better understanding of HIV-1 latency and suggest that inhibition of Naf1 activity to activate latently HIV-1-infected cells may be a potential therapeutic strategy. IMPORTANCE HIV-1 latency is characterized mainly by a reversible silencing of LTR promoter-driven transcription of an integrated provirus. Cellular and viral proteins regulating LTR activity contribute to the modulation of HIV-1 latency. In this study, we found that the host protein Naf1 inhibited HIV-1 LTR-driven transcription of HIV genes and contributed to the maintenance of HIV-1 latency. Our findings provide new insights into the effects of host modulation on HIV-1 latency, which may lead to a potential therapeutic strategy for HIV persistence by targeting the Naf1 protein.

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Confirmation of TNIP1 and IL23A as susceptibility loci for psoriatic arthritis

Cited by 112 publications

References 23 publications

ABIN1 Dysfunction as a Genetic Basis for Lupus Nephritis

ABIN1 Dysfunction as a Genetic Basis for Lupus Nephritis

Innate Immunity in Coronary Disease. The Role of Interleukin-12 Cytokine Family in Atherosclerosis

Naf1 Regulates HIV-1 Latency by Suppressing Viral Promoter-Driven Gene Expression in Primary CD4 ⁺ T Cells

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Confirmation of TNIP1 and IL23A as susceptibility loci for psoriatic arthritis

Cited by 112 publications

References 23 publications

ABIN1 Dysfunction as a Genetic Basis for Lupus Nephritis

ABIN1 Dysfunction as a Genetic Basis for Lupus Nephritis

Innate Immunity in Coronary Disease. The Role of Interleukin-12 Cytokine Family in Atherosclerosis

Naf1 Regulates HIV-1 Latency by Suppressing Viral Promoter-Driven Gene Expression in Primary CD4 + T Cells

Contact Info

Product

Resources

About

Naf1 Regulates HIV-1 Latency by Suppressing Viral Promoter-Driven Gene Expression in Primary CD4 ⁺ T Cells