Specific association of a CLEC16A/KIAA0350 polymorphism with NOD2/CARD15− Crohn's disease patients

Márquez, Ana; Varadé, Jezabel; Robledo, Gema; Martínez, Alfonso; Mendoza, Juan L.; Taxonera, Carlos; Fernández‐Arquero, Miguel; Dı́az-Rubio, Manuel; Gómez‐García, María; López–Nevot, Miguel A.; Concha, Emilio G. de la; Martı́n, Javier; Urcelay, Elena

doi:10.1038/ejhg.2009.50

Cited by 46 publications

(37 citation statements)

References 23 publications

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“…Despite the fact that there is an increasingly list of genetic factors associated with IBD, it is estimated that the current number of loci associated with IBD represents only a small fraction of the genetic risk. Thus, additional genetic contributions clearly remain to be discovered [3,[5][6][7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 93%

STAT4 gene influences genetic predisposition to ulcerative colitis but not Crohn's disease in the Spanish population: A replication study

et al. 2010

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Section: Introductionmentioning

confidence: 93%

STAT4 gene influences genetic predisposition to ulcerative colitis but not Crohn's disease in the Spanish population: A replication study

et al. 2010

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“…135 Furthermore, recent genetic analysis has demonstrated that an SNP in the region of CLEC16A (which encodes a protein containing a C-type lectin domain) was associated with CD patients specifically lacking the three known CD-associated NOD2/CARD15 mutations. 136 Secretory IgA (sIgA)…”

Section: Enterocyte Secretory Functionmentioning

confidence: 99%

Function of the intestinal epithelium and its dysregulation in inflammatory bowel disease

Henderson

Limbergen

Schwarze

et al. 2011

Inflammatory Bowel Diseases

109

107

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The intestinal epithelium not only acts as a physical barrier to commensal bacteria and foreign antigens but is also actively involved in antigen processing and immune cell regulation. The inflammatory bowel diseases (IBDs) are characterized by inflammation at this mucosal surface with well-recognized defects in barrier and secretory function. In addition to this, defects in intraepithelial lymphocytes, chemokine receptors, and pattern recognition receptors promote an abnormal immune response, with increased differentiation of proinflammatory cells and a dysregulated relationship with professional antigen-presenting cells. This review focuses on recent developments in the structure of the epithelium, including a detailed account of the apical junctional complex in addition to the role of the enterocyte in antigen recognition, uptake, processing, and presentation. Recently described cytokines such as interleukin-22 and interleukin-31 are highlighted as is the dysregulation of chemokines and secretory IgA in IBD. Finally, the effect of the intestinal epithelial cell on T effector cell proliferation and differentiation are examined in the context of IBD with particular focus on T regulatory cells and the two-way interaction between the intestinal epithelial cell and certain immune cell populations.

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“…[1][2][3] Multiple replication and candidate gene studies have verified this region as being disease associated in T1D and MS, and association with CLEC16A has also been found in anti-cyclic citrullinated peptide (CCP) negative rheumatoid arthritis, juvenile idiopathic arthritis, Addison's disease and NOD2-negative Crohn's disease. [4][5][6][7][8][9] The association of CLEC16A SNPs across multiple immune-mediated diseases and the observation that the gene is almost uniquely expressed on immune cells, make a common effect on autoimmunity likely. The CLEC16A protein belongs to the C-type lectin family whose immune functions include differentiation of self versus non-self glycoproteins and the induction of the appropriate immune response.…”

Section: Introductionmentioning

confidence: 99%

“…The originally described MSassociated SNP rs6498169 has been shown to be associated with anti-CCP-negative rheumatoid arthritis and juvenile idiopathic arthritis, but not anti-CCP-positive rheumatoid arthritis, Addison's disease and NOD2-negative Crohn's disease. 5,8,16 Vice versa the T1D SNPs rs2903692 and rs12708716 have shown association with NOD2-negative Crohn's and Addison's disease, respectively. 5,8 Thus to date, MS is the only disease described to be associated with both rs6498169 and the LD block containing the four T1D associated SNPs.…”

Section: Introductionmentioning

confidence: 99%

“…5,8,16 Vice versa the T1D SNPs rs2903692 and rs12708716 have shown association with NOD2-negative Crohn's and Addison's disease, respectively. 5,8 Thus to date, MS is the only disease described to be associated with both rs6498169 and the LD block containing the four T1D associated SNPs. The only fine-mapping study of CLEC16A performed in MS so far is an Australian study (n ¼ 1146 cases and n ¼ 1309 controls) of several MS risk genes, where 44 tagging SNPs in the CLEC16A gene pointed towards rs6498169, the most significantly associated CLEC16A SNP in the original IMSGC GWAS.…”

Section: Introductionmentioning

confidence: 99%

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Exploring the CLEC16A gene reveals a MS-associated variant with correlation to the relative expression of CLEC16A isoforms in thymus

Ban

År

et al. 2010

Genes Immun

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Genomewide association studies have implicated the CLEC16A gene in several autoimmune diseases, including multiple sclerosis (MS) and type 1 diabetes. However, the most associated single-nucleotide polymorphism (SNP) varies, and causal variants are still to be defined. In MS, two SNPs in partial linkage disequilibrium with each other, rs6498169 and rs12708716, have been validated at genomewide significance level. To explore the CLEC16A association in MS in more detail, we genotyped 57 SNPs in 807 Norwegian MS patients and 1027 Norwegian controls. Six highly associated SNPs emerged and were then replicated in two large independent sample sets (Norwegian and British), together including 1153 MS trios, 2308 MS patients and 4044 healthy controls. In combined analyses, SNP rs12708716 gave the strongest association signal in MS (P ¼ 5.3 Â 10 À8 , odds ratio 1.18, 95% confidence interval ¼ 1.11-1.25), and was found to be superior to the other SNP associations in conditional logistic regression analyses. Expression analysis revealed that rs12708716 genotype was significantly associated with the relative expression levels of two different CLEC16A transcripts in thymus (P ¼ 0.004), but not in blood, possibly implying a thymus-or cell-specific splice regulation.

show abstract

Specific association of a CLEC16A/KIAA0350 polymorphism with NOD2/CARD15− Crohn's disease patients

Cited by 46 publications

References 23 publications

STAT4 gene influences genetic predisposition to ulcerative colitis but not Crohn's disease in the Spanish population: A replication study

STAT4 gene influences genetic predisposition to ulcerative colitis but not Crohn's disease in the Spanish population: A replication study

Function of the intestinal epithelium and its dysregulation in inflammatory bowel disease

Exploring the CLEC16A gene reveals a MS-associated variant with correlation to the relative expression of CLEC16A isoforms in thymus

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