Frequencies of Genetic Polymorphisms of TLR4 and CD14 and of HLA‐DQ Genotypes in Children With Celiac Disease, Type 1 Diabetes Mellitus, or Both

Dezsőfi, Antal; Szebeni, Beáta; Cs, Hermann; Kapitány, Anikó; Veres, Gábor; Sipka, Sándor; Körner, Anna; Madácsy, László; Korponay-Szabó, Ilma Rita; Rajczy, Katalin; Arató, András

doi:10.1097/mpg.0b013e31816de885

Cited by 32 publications

(26 citation statements)

References 45 publications

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“…The increased CD14 expression, in presence of c.-159C4T T allele and in particular of the TT genotype, may lead to an increased activation of the TLR4 receptor, thereby eliciting a stronger reaction to bacterial infection. 38 The consequent inflammation in the jejunal mucosa may disrupt the intestinal permeability barrier, leading to an increased gluten load in the lamina propria, where most of the gluten-reactive lymphocytes are situated, thus explaining the increased susceptibility to CD found in individuals with the c.-159C4T TT genotype 25 and the protective effect of the CC genotype we reported.…”

Section: Discussionmentioning

confidence: 71%

CD14 polymorphisms correlate with an augmented risk for celiac disease in Italian patients

et al. 2012

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Celiac disease (CD) is a T-cell-mediated chronic inflammatory disease characterized by autoimmune, immunological and environmental components, where genetic factors in addition to the main known risk factors (gliadin and human leukocyte antigen (HLA)-DQ haplotypes) are supposed to be involved. CD14 is a multifunctional receptor involved in the bacterial lipopolysaccharidesdependent signal transduction. The CD14 gene maps on the long arm of chromosome 5 (5q22-q32), a 'hotbed' region for CD; promoter polymorphisms are known to influence its expression. In this study we analyzed three CD14 promoter polymorphisms (c.-1359G4T, c.-1145A4G and c.-159C4T, ) in 938 CD Italian patients and 533 healthy controls, with known HLA-DQ haplotypes, with the aim of evaluating their possible association with the disease. The c.-1145A4G G and c.-159C4T T alleles (as well as the combination of the two alleles in the GT haplotype), were identified as susceptibility factors for CD development, being significantly more frequent in CD patients than in healthy controls. This association was also confirmed when the analysis was restricted to only those subjects characterized by HLA-DQ risk haplotypes. Our results indicate the involvement of CD14 gene polymorphisms in the susceptibility to CD.

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Section: Discussionmentioning

confidence: 71%

CD14 polymorphisms correlate with an augmented risk for celiac disease in Italian patients

et al. 2012

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“…41 Homozygosis for HLADQ2 confers the highest risk to develop CD, while homozygosis for HLADQ8 confers the highest risk for T1DM. 42 HLADQ2, however, has been found to be the most frequent allele in the patients with both CD and T1DM. [43][44][45] The HLADQ8 transdimer recognizes gluten and binds efficiently both gliadin peptides and also peptides derived from glutamic acid decarboxylase and islet cells antibody (IA-2).…”

Section: Pathogenesis Geneticsmentioning

confidence: 99%

“…72 Similarly, the TLR3 and TLR4 genes, which play an important role in the innate immune response triggered by viral infection, are responsible for the development of both T1DM and CD. 42,73,74 …”

Section: Environmentmentioning

confidence: 99%

Dietary gluten and the development of celiac disease and type 1 diabetes

Ciacci¹,

Zingone²

2016

NDS

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Abstract:The objective of this study was to perform a review of the present knowledge on the epidemiology and pathogenesis of the association between celiac disease (CD) and type 1 diabetes mellitus (T1DM). Results from this review show that the estimated prevalence rate of CD in T1DM ranges from 4% to 11.5%, which seems higher in children than in adults, while there is no sex predominance in the prevalence of CD in T1DM. On the basis of the previous literature, screening for CD should be considered at diabetes diagnosis in all subjects and again within 2 and 5 years after diagnosis, even in the absence of symptoms. The anti-islet antibodies detection test, instead, is not recommended in CD, just as in the general population, except for CD patients having a relative with T1DM. Both genes and environmental factors seem to play a role in this association. HLADQ2 has been found to be the most frequent allele in the patients with both CD and T1DM, while gluten may be considered the trigger that induces the production of autoantibodies and the development, in genetically predisposed individuals, of both diseases.

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“…Activation of these receptors contributes to the increased expression of inflammatory cytokines, initiating infiltration of lymphocytes into the lamina propria, villous atrophy, crypt hyperplasia, which are all characteristic for CD [15]. Also toxic gliadin fragments may induce TLR signaling and regulates the expression of tight junction proteins.…”

mentioning

confidence: 99%

Role of the Microbiome in Celiac Disease

Béres

Sziksz

Vannay

et al. 2016

IJCD

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Microbiome is the community of commensal, symbiotic and pathogenic microorganism that share our human body space. Intestinal microbiota has a defensive role in human health, it is implicated in metabolic and nutritional processes and plays an important role in the pathophysiology of several diseases. In recent years special attention has been paid to investigations targeting the changes of intestinal microbiome in various gastrointestinal disorders including inflammatory bowel disease, infectious colitis and celiac disease (CD). The aim of our present review is to summarize the role of the microbiome in CD and the changes of its composition in the intestine of patients suffering from CD.

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Frequencies of Genetic Polymorphisms of TLR4 and CD14 and of HLA‐DQ Genotypes in Children With Celiac Disease, Type 1 Diabetes Mellitus, or Both

Cited by 32 publications

References 45 publications

CD14 polymorphisms correlate with an augmented risk for celiac disease in Italian patients

CD14 polymorphisms correlate with an augmented risk for celiac disease in Italian patients

Dietary gluten and the development of celiac disease and type 1 diabetes

Role of the Microbiome in Celiac Disease

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