Celiac Disease: Strongly Heritable, Oligogenic, but Genetically Complex

King, A; Ciclitira, Paul J.

doi:10.1006/mgme.2000.3067

Cited by 32 publications

(8 citation statements)

References 46 publications

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“…The genetics involved in the development of CD is very complex, with evidence for the participation of multiple intrinsic (genetic) and extrinsic (environmental) factors34, hence, a single genetic variant is generally inadequate and failed to interpret the risk of this disease. Notwithstanding, the significant findings achieved from this study, we still have to acknowledge some of the limitations of this meta-analysis.…”

Section: Discussionmentioning

confidence: 99%

TNF-α -308 G > A (rs1800629) Polymorphism is Associated with Celiac Disease: A Meta-analysis of 11 Case-Control Studies

Khan

Mandal

Jawed

et al. 2016

Sci Rep

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Celiac disease (CD; also known as celiac sprue, gluten-sensitive enteropathy, and nontropical sprue) is a chronic inflammatory autoimmune disorder characterized by abnormalities in the small intestine caused by permanent intolerance to dietary gluten or related proteins from wheat and rye 1 . Although few CD patients may suffer primarily from gastrointestinal symptoms, CD may be related with extra-intestinal disorders 2 . Genetic, immunological and environmental factors have been attributed for the disease. Till date, the etiology of CD has not yet been fully elucidated. However, CD has shown a strong genetic relation with HLA (human leucocyte antigen) class II gene, contributing no more than 40% to the disease risk, which shows involvement of genetic components in the development of CD 3,4 . Recently published genome-wide association study (GWAS) has identified several non-HLA genes as new susceptibility factors for CD. So far, 39 loci with 57 independent association signals have been defined and many of these loci harbour genes associated with immunity 5

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Section: Discussionmentioning

confidence: 99%

TNF-α -308 G > A (rs1800629) Polymorphism is Associated with Celiac Disease: A Meta-analysis of 11 Case-Control Studies

Khan

Mandal

Jawed

et al. 2016

Sci Rep

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“…It is a multifactorial disease in which HLA genes, non-HLA genes, and environmental factors play a role in its pathogenesis [12,13]. More than 95% of celiac patients share one of HLA class II molecules, namely, HLA DQ2, DR3, and B8 haplotypes [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

The response to hepatitis B vaccine: does it differ in celiac disease?

Ertem¹,

Gönen²,

Tanıdır

et al. 2010

European Journal of Gastroenterology & Hepatology

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“…The majority of the remainder of patients express the rarer antigen DQ8. 3 All small intestinal gluten sensitive T cell clones identified to date are DQ restricted, reflecting the critical role of these molecules in gliadin antigen presentation. 4 It has been suggested that the T cell response may be dominated by two overlapping immunodominant epitopes.…”

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confidence: 99%

Investigation of the putative immunodominant T cell epitopes in coeliac disease

Ellis

Pollock²,

Engel³

et al. 2003

Gut

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Background: Coeliac disease (CD) is an enteropathy mediated by gluten specific T cells which secrete interferon γ (IFN-γ) when stimulated by gluten peptides presented by HLA-DQ2 or DQ8 molecules. Residues 62-75 of α 2 gliadin have been proposed as the immunodominant epitope in the majority of CD patients. Deamidation by tissue transglutaminase (tTG) of the glutamine (Q) at position 65 to glutamic acid (E) is essential for T cell stimulation. Aims: To investigate the antigenicity of this peptide and to establish whether its T cell activating properties can be downregulated by the formation of altered peptide ligands. Patients: Individuals with known CD. Methods: Peptide G4 corresponding to α 2 gliadin residues 62-75, Q-E65 and analogues, substituting each amino acid, except E65, in turn for alanine residues, were synthesised. Small intestinal biopsies were obtained from patients. Biopsies were cultured overnight with a peptic/tryptic digest of gliadin (PTG). Lymphocytes were cultured and restimulated with tTG treated PTG. A T cell line was cloned and clones tested for stimulation and IFN-γ production in response to G4 and its analogues. Results: Some high activity clones were isolated with, for example, a stimulation index (SI) of 15 to G4 and secreting 327 pg/ml of IFN-γ. Substitution of amino acids at several positions abolished or downregulated stimulation and IFN-γ production. Conclusions: Peptide G4 is highly immunogenic. Certain amino acid substitutions in peptide G4 abolish T cell reactivity while others are partial agonists which may have potential in immunomodulation in this condition.

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Celiac Disease: Strongly Heritable, Oligogenic, but Genetically Complex

Cited by 32 publications

References 46 publications

TNF-α -308 G > A (rs1800629) Polymorphism is Associated with Celiac Disease: A Meta-analysis of 11 Case-Control Studies

TNF-α -308 G > A (rs1800629) Polymorphism is Associated with Celiac Disease: A Meta-analysis of 11 Case-Control Studies

The response to hepatitis B vaccine: does it differ in celiac disease?

Investigation of the putative immunodominant T cell epitopes in coeliac disease

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