Inflammatory bowel disease is associated with a TNF polymorphism that affects an interaction between the OCT1 and NF-kappaB transcription factors

Heel, David A. van; Udalova, Irina A.; Silva, Arjuna P. De; McGovern, Dermot P.; Kinouchi, Yoshitaka; Hull, Jeremy; Lench, Nicholas J.; Cardon, Lon R.; Carey, Alisoun H.; Jewell, D P; Kwiatkowski, Dominic P.

doi:10.1093/hmg/11.11.1281

Cited by 263 publications

(166 citation statements)

References 53 publications

Supporting

Mentioning

158

Contrasting

Order By: Relevance

“…Thus, the association between TNF-␣ polymorphisms, its production, and disease has been studied by a number of investigators. While in a number of studies it was concluded that such an association exists (57)(58)(59)(60)(61), other studies did not find evidence for this (62)(63)(64). This is not surprising since factors modulating the cytokine synthesis or molecules mediating its activity such as TNF receptors are also expected to impact TNF-␣-dependent functions.…”

Section: Discussionmentioning

confidence: 99%

Toll-like Receptor 9 Regulates Tumor Necrosis Factor-α Expression by Different Mechanisms

Amcheslavsky

Zou

Bar‐Shavit

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Toll-like Receptor 9 Regulates Tumor Necrosis Factor-α Expression by Different Mechanisms

Amcheslavsky

Zou

Bar‐Shavit

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…The current model suggests that in the presence of the minor T allele, a novel transcription factor binding site (OCT-1) is generated at the promoter region of the TNFA gene, immediately next to a preexisting NF-B binding site. As a result, an altered regulation of the gene might be generated in response to various stimuli, which involves the activation of NF-B [63]. The protective nature of the -857T allele has also been suggested by reports on the pathogenesis of other chronic inflammatory diseases, suggesting the general importance of this SNP in the regulation of TNFA gene expression [63,64].…”

Section: The Role Of Tnf-␣ In the Predisposition To Acnementioning

confidence: 95%

Studying the genetic predisposing factors in the pathogenesis of acne vulgaris

Szabó

Kemény

2011

Human Immunology

View full text Add to dashboard Cite

A B S T R A C TAcne is one of the most common dermatologic diseases in the developed regions of the world, affecting a large percentage of the population. Despite the great improvement in the number and quality of studies of the molecular etiology of this disease in the past 3 decades, the detailed molecular pathogenesis and the cause of the large individual variations in severity of skin symptoms remain unknown. The roles of genetic inheritance and special genetic susceptibility and protective factors have been suggested for over 100 years, but their identification and determination started only in the 1990s. To date, only a small number of genetic polymorphisms affecting the expression and/or function of a handful of genes have been investigated. This review surveys the major findings of the classic and molecular genetic studies that have been conducted in this field, draws conclusions, and indicates how the available data help our current understanding of the pathogenesis of this common skin disease. ᭧

show abstract

“…The next 5 years will hopefully extend this work by addressing missing heritability and elucidating the molecular mechanisms underlying innate immunodeficiency. It may be that improved or augmented genetic screening tools will be able to detect risk alleles of lower frequency than those currently described [116], and further study of epistasis (gene-gene interactions [139,140]) may be key to understanding the pathogenesis of complex phenotypes. There is potentially a wealth of knowledge contained within the known IBD loci [121], and fine mapping of the genes within these regions will identify novel genetic influences.…”

Section: Expert Commentary and Five-year Viewmentioning

confidence: 99%

Crohn’s disease as an immunodeficiency

Hayee

Rahman

Sewell

et al. 2010

Expert Review of Clinical Immunology

View full text Add to dashboard Cite

The pathogenesis of Crohn's disease (CD) has widely been regarded as the consequence of a dysregulated T-cell-mediated response to intestinal microbes, and the majority of the worldwide research effort has focused on characterizing and treating the chronic inflammatory phase of the disease. However, recent molecular biological and clinical investigations indicate that CD is actually a primary immunodeficiency. At first counter-intuitive, the apparent paradox of a pathogenic innate immune defect can be linked mechanistically to the granulomatous chronic inflammation characteristic of the disease. Genome-wide association studies have corroborated the involvement of innate immune dysfunction in the pathogenesis of CD, but less than 20% of the heritable risk is accounted for. By contrast, in vitro and in vivo stimulation of the immune system has highlighted novel areas of interest that may lead to the development of targeted therapeutic and diagnostic tools. Keywordsbacteria; Crohn's disease; immunodeficiency; innate immunity; macrophage; neutrophil Established intestinal lesions in Crohn's disease (CD) contain a massive, mixed inflammatory cell infiltrate associated with a complex storm of cytokines in a selfperpetuating, chronic inflammatory response [1][2][3]. Most research to date has focused on the the immunological characteristics of established lesions and drawn inferences about their initiation. The predominance of a classically Th1-associated cytokine profile in these lesions led to the assumption that T lymphocytes were central to the initial pathogenesis. More recently, the role of regulatory (Treg) FoxP3 + and IL-23-induced responsive Th17-type T lymphocytes has gained popularity [2,4,5]. Treg cell populations are diminished in patients with CD [6] and, although the hypothesis of CD as an immunodeficiency does not necessarily exclude defects in T-cell function, to date, no convincing intrinsic (primary) defect has been identified to implicate these cells in the pathogenesis of human CD.The hypothesis that immunodeficiency underpins the development of CD seems, at first, to be in direct contrast with histological observations of established intestinal lesions and the † Author for correspondence: Tel.: +44 207 679 6170 Fax: +44 207 679 0967 b.hayee@nhs.net. Financial & competing interests disclosure The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Europe PMC Funders Group Association between immunodeficiency diseases & CDThere is a well-known and strong association between primary immunodeficiency disorders and non-infectious granulomatous intestinal inflammation. Chronic granulomatous disease (CGD), glycogen storage disease type 1b, leukocyte adhesion deficiency, Chediak-Higashi and Hermansky-Pudlak syndromes are all strongly associated with intestinal inflammation that is indistinguishable from CD [...

show abstract

Inflammatory bowel disease is associated with a TNF polymorphism that affects an interaction between the OCT1 and NF-kappaB transcription factors

Cited by 263 publications

References 53 publications

Toll-like Receptor 9 Regulates Tumor Necrosis Factor-α Expression by Different Mechanisms

Toll-like Receptor 9 Regulates Tumor Necrosis Factor-α Expression by Different Mechanisms

Studying the genetic predisposing factors in the pathogenesis of acne vulgaris

Crohn’s disease as an immunodeficiency

Contact Info

Product

Resources

About