A comprehensive screen for SNP associations on chromosome region 5q31–33 in Swedish/Norwegian celiac disease families

Amundsen, Silja Svanstrøm; Adamovic, Svetlana; Hellqvist, Åsa; Nilsson, Staffan; Gudjonsdottir, Audur H.; Ascher, Henry; Ek, Johan; Larsson, Kristina; Wahlström, Jan; Lie, Benedicte A.; Sollid, Ludvig M.; Naluai, Åsa Torinsson

doi:10.1038/sj.ejhg.5201870

Cited by 14 publications

(16 citation statements)

References 27 publications

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“…83 -87 In addition, a large fine-mapping study failed to single out a strong susceptibility candidate. 88 There were several genes showing nominal association in this Norwegian/Swedish family sample but no single association could explain the large linkage peak found in the same sample. 88 Unless, there are regions inadequately covered due to, for example, copy number variation, these finding suggests that there is too much allelic heterogeneity or too many founder haplotypes to pin a gene down.…”

Section: Fine-mapping and Positional Candidates On Chromosomes 5 And 19mentioning

confidence: 71%

Searching for genes influencing a complex disease: the case of coeliac disease

et al. 2007

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Recently, a few genes have been reported to be causative in inflammatory diseases. Still, we are waiting for the vast majority to be discovered. New tools for genotyping and statistical analysis have been developed and emphasis has been put on study design. Coeliac disease (CD) is a disorder, where prolamins in dietary wheat gluten and related proteins from rye or barley are not tolerated. It is one of the most common chronic diseases in humans exceeding a population prevalence of 1%. In this article, we will summarise what is currently known about the genetics influencing CD with the emphasis on the non-HLA genetic component. We will discuss some difficulties when searching for susceptibility genes in disorders with complex inheritance patterns.

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Section: Fine-mapping and Positional Candidates On Chromosomes 5 And 19mentioning

confidence: 71%

Searching for genes influencing a complex disease: the case of coeliac disease

et al. 2007

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“…Previously, high prevalence of anti-I2 and anti-OmpW antibodies has been reported in children and adults with Crohn's disease. 12,17,47 . Interestingly, ninety per cent of CD patients showed positive seroreactivity at least one of microbial antigens (ASCA, I2, OmpW) tested in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, chromosomal region 5q31 has demonstrated to link with both CD and Crohn's disease in genome-wide studies. [16][17][18] Commensal luminal bacteria are inducing dysregulated mucosal immune responses which may contribute to Crohn's disease pathogenesis. 19 Indeed, a number of microorganisms and their products have been implicated in Crohn's disease shown in studies of proving their presence in mucosal lesions and the occurrence of serologic anti-microbial host responses (e.g., enteroadhesive E. coli, MAP, P. fluorescens, B. caccae, ASCA).…”

Section: Introductionmentioning

confidence: 99%

Elevated Serum Anti-Saccharomyces cerevisiae, Anti-I2 and Anti-OmpW Antibody Levels in Patients with Suspicion of Celiac Disease

et al. 2008

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Objectives-Expression of anti-Saccharomyces Cerevisiae antibodies (ASCA) identifies patients and individuals at risk for Crohn's disease and has also been reported in 40-60% of Celiac disease (CD) cases, suggesting a role of host response to enteric microbiota in the development of inflammatory lesions. In this prospective study in patients with suspicion of CD, we evaluate the frequency and association of ASCA to serological responses for other host microbial targets formally associated with Crohn's disease, including the P.fluorescens associated sequence I2 and a Bacteroides caccae TonB-linked outermembrane protein, OmpW.Methods-Small bowel mucosal biopsies were taken from 242 patients with CD suspicion, their sera were tested for antibodies to tissue transglutaminase (tTG), ASCA, I2 and OmpW. 80 adult healthy blood donors were used as controls.Results-The diagnosis of CD was confirmed on biopsy in 134 cases. The occurence of ASCA and I2 positivity was significantly higher in adult CD patients as compared to patients with non-CD disease. Anti-I2 levels in the sera were significantly higher in adult CD patients compared to non-CD disease or the controls and anti-OmpW levels in CD and non-CD patients when compared to controls. Positive seroreactivity to OmpW seemed to increase with the age. 90% of CD patients were seropositive for at least one microbial antigen tested.Conclusions-This study demonstrates a mosaic of disease-related serological responses to microbial antigens in patients with CD. Immune responses to commensal enteric bacteria may play a role in the small intestine mucosal damage in CD.

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“…coli BL-21 (Stratagene, La Jolla, CA, USA) strains were used for all cloning and recombinant expression experiments. I2-GST and OmpW were produced by using previously reported antigen purification techniques [18, 19]. Sera were analyzed with IgA enzymelinked immunosorbent assays (ELISA) to I2 and OmpW.…”

Section: Methodsmentioning

confidence: 99%

Serological Responses to Microbial Antigens in Celiac Disease Patients During a Gluten-Free Diet

et al. 2008

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Background Immunoglobulin A (IgA) autoantibodies to tissue transglutaminase (tTG) are commonly used for screening and diagnosing of celiac disease (CD). Seroreactivity for anti-Saccharomyces cerevisiae antibody (ASCA) and bacterial antigens have also been detected in CD patients. The aim of this study was to examine prospectively serologic responses to microbial targets in adult CD patients at the time of diagnosis and during a gluten-free diet (GFD). Further, we wanted to evaluate whether these serologic specificities could provide new tools for the follow-up of CD patients. Methods Data on 55 adult biopsy-proven CD patients were available for follow-up study. Upper gastrointestinal endoscopy was performed on all patients. Sera from patients were tested for antibodies to tTG and ASCA and additionally analyzed with IgA enzyme-linked immunosorbent assays to Pseudomonas fluorescens-associated sequence, I2, and to a Bacteroides caccae TonB-linked outer membrane protein, OmpW. Results At the time of diagnosis, 91% of CD cases were positive for tTG and 49% for ASCA; positive seroreactivity to I2 was found in 86% and to OmpW in 60% of CD patients at the time of diagnosis. The frequency of seropositivity and serum levels of these antibodies decreased during GFD. Moreover, we found that the decline in the serum levels was significant in all of these markers (p<0.005). Interestingly, we also found that serum levels of ASCA correlated with the grade of mucosal morphology (p=0.021), as the ASCA serum levels declined in accordance with mucosal healing. Conclusions Commensal enteric bacteria seem to play a role in the small intestinal mucosal damage in CD. This was proven by the serological responses to different microbial antigens shown in this study. Serum levels of ASCA, anti-I2, and anti-OmpW antibodies decreased significantly during GFD, indicating that these serologic markers are gluten dependent in CD patients. These specificities could provide new tools in the follow-up of CD patients.

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A comprehensive screen for SNP associations on chromosome region 5q31–33 in Swedish/Norwegian celiac disease families

Cited by 14 publications

References 27 publications

Searching for genes influencing a complex disease: the case of coeliac disease

Searching for genes influencing a complex disease: the case of coeliac disease

Elevated Serum Anti-Saccharomyces cerevisiae, Anti-I2 and Anti-OmpW Antibody Levels in Patients with Suspicion of Celiac Disease

Serological Responses to Microbial Antigens in Celiac Disease Patients During a Gluten-Free Diet

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