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Genotype–phenotype associations of polymorphisms within the gene locus of NOD-like receptor pyrin domain containing 3 in Swiss inflammatory bowel disease patients

Yoganathan, Priyatharsan ; Rossel, Jean-Benoit ; Jordi, Sebastian Bruno Ulrich ; [et al.]

Springer Science and Business Media LLC ; 2021

In: BMC Gastroenterology Vol. 21, No. 1 ( 2021-08-03)

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In: BMC Gastroenterology, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-08-03)

Abstract: Genetic variations within the regulatory region of the gene encoding NOD-like receptor pyrin domain containing 3 ( NLRP3 ) have been associated with Crohn’s Disease (CD). NLRP3 is part of the NLRP3-inflammasome that mediates the maturation of IL-1β and IL-18. Carrying the major allele of the single nucleotide polymorphisms (SNPs) rs10733113, rs4353135 and rs55646866 is associated with an increased risk for CD. We here studied the impact of these polymorphisms on clinical characteristics in patients of the Swiss IBD Cohort Study (SIBDCS). Methods We included 981 Crohn’s disease (CD) patients and 690 ulcerative colitis (UC) patients of the SIBDCS. We analyzed whether three CD-associated NLRP3 polymorphisms have an impact on the clinical disease course in these patients. Results In CD patients presence of the major allele (G) of rs10733113 was associated with less surgeries and lower maximal CDAI and a similar trend was observed for rs55646866 and rs4353135. Presence of the major allele of all three SNPs was negatively correlated to maximal CDAI. In UC patients homozygous genotype for the major allele (CC) for rs55646866 was associated with a higher age at diagnosis and a higher MTWAI index. Homozygous genotype for the major allele of all three polymorphisms was associated with a higher number of ambulatory visits and longer hospital stays. Conclusions In CD patients presence of the major allele of all three polymorphisms was associated with markers of a less severe disease course, while in UC the homozygous genotype for all major alleles suggested a more severe disease activity.

Type of Medium: Online Resource

ISSN: 1471-230X

URL: Article

DOI: 10.1186/s12876-021-01880-9

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 2041351-8

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Lifestyle factors associated with inflammatory bowel disease: data from the Swiss IBD cohort study

Lautenschlager, Severin A. ; Barry, Mamadou Pathé ; Rogler, Gerhard ; [et al.]

Springer Science and Business Media LLC ; 2023

In: BMC Gastroenterology Vol. 23, No. 1 ( 2023-03-12)

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In: BMC Gastroenterology, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-03-12)

Abstract: Various environmental risk factors have been associated with the pathogenesis of inflammatory bowel disease. In this study we aimed to identify lifestyle factors that affect the onset of Crohn’s disease and ulcerative colitis. Methods 2294 patients from the Swiss IBD Cohort Study received a questionnaire regarding physical activity, nutritional habits and status of weight. In addition, a control group was formed comprising patients’ childhood friends, who grew up in a similar environment. Results Overall, 1111 questionnaires were returned (response rate: 48.4%). Significantly more patients with inflammatory bowel disease reported no regular practice of sport during childhood and beginning of adulthood compared to the control group ( p = 0.0001). No association between intake of refined sugar and onset of inflammatory bowel disease was observed. More patients with Crohn’s disease compared to ulcerative colitis and controls suffered from overweight during childhood (12.8% vs. 7.7% and 9.7%, respectively; p = 0.027). Conclusions Our study underlines the relevance of environmental factors in the development of inflammatory bowel disease. Our results imply a protective effect of physical activity regarding the onset of inflammatory bowel disease.

Type of Medium: Online Resource

ISSN: 1471-230X

URL: Article

DOI: 10.1186/s12876-023-02692-9

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

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Author Correction: Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Serra, Eva Gonçalves ; Schwerd, Tobias ; Moutsianas, Loukas ; [et al.]

Springer Science and Business Media LLC ; 2022

In: Nature Communications Vol. 13, No. 1 ( 2022-06-22)

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In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-06-22)

Type of Medium: Online Resource

ISSN: 2041-1723

URL: Article

DOI: 10.1038/s41467-022-31010-2

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2022

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Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Serra, Eva Gonçalves ; Schwerd, Tobias ; Moutsianas, Loukas ; [et al.]

Springer Science and Business Media LLC ; 2020

In: Nature Communications Vol. 11, No. 1 ( 2020-02-21)

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In: Nature Communications, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2020-02-21)

Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences ( XIAP, CYBA, SH2D1A, PCSK1 ). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB . The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P 〈 4 × 10 −10 ), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P 〈 5 × 10 −10 ). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.

Type of Medium: Online Resource

ISSN: 2041-1723

URL: Article

DOI: 10.1038/s41467-019-14275-y

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2020

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Loss of the branched-chain amino acid transporter CD98hc alters the development of colonic macrophages in mice

Wuggenig, Philipp ; Kaya, Berna ; Melhem, Hassan ; [et al.]

Springer Science and Business Media LLC ; 2020

In: Communications Biology Vol. 3, No. 1 ( 2020-03-18)

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In: Communications Biology, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2020-03-18)

Abstract: Comprehensive development is critical for gut macrophages being essential for the intestinal immune system. However, the underlying mechanisms of macrophage development in the colon remain elusive. To investigate the function of branched-chain amino acids in the development of gut macrophages, an inducible knock-out mouse model for the branched-chain amino acid transporter CD98hc in CX3CR1 + macrophages was generated. The relatively selective deletion of CD98hc in macrophage populations leads to attenuated severity of chemically-induced colitis that we assessed by clinical, endoscopic, and histological scoring. Single-cell RNA sequencing of colonic lamina propria macrophages revealed that conditional deletion of CD98hc alters the “monocyte waterfall”-development to MHC II + macrophages. The change in the macrophage development after deletion of CD98hc is associated with increased apoptotic gene expression. Our results show that CD98hc deletion changes the development of colonic macrophages.

Type of Medium: Online Resource

ISSN: 2399-3642

URL: Article

DOI: 10.1038/s42003-020-0842-3

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2020

detail.hit.zdb_id: 2919698-X

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Effects of anti-TNF therapy and immunomodulators on anxiety and depressive symptoms in patients with inflammatory bowel disease: a 5-year analysis

Siebenhüner, Alexander R. ; Rossel, Jean-Benoît ; Schreiner, Philipp ; [et al.]

SAGE Publications ; 2021

In: Therapeutic Advances in Gastroenterology Vol. 14 ( 2021-01), p. 175628482110337-

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In: Therapeutic Advances in Gastroenterology, SAGE Publications, Vol. 14 ( 2021-01), p. 175628482110337-

Abstract: Anxiety and depression are prevalent in patients with inflammatory bowel diseases (IBD), especially during IBD flares. IBD therapies can profoundly affect the mood of patients with IBD. We aimed to determine the long-term impact of anti-tumor necrosis factor (anti-TNF) and immunomodulators (IM) on anxiety and depressive symptoms in IBD patients. Methods: We compared three treatment groups with IM only (group A), anti-TNF ± IM (group B) and no such therapy (group C). Patients completed the hospital anxiety and depression scale (HADS) at 1 year, 3 years, and 5 years after start of treatment. Results: In total, 581 patients with IBD (42.9% Crohn’s disease, 57.1% ulcerative colitis/IBD unclassified) participated in this study. Effects of treatment were analyzed in a mixed effects model, with and without correction for confounders. Compared with group C, group B showed a significant treatment-related improvement in both anxiety and depressive symptoms within the first 2.5 years and also thereafter. Group A showed a significant long-term improvement of anxiety and both short-term and long-term improvement in depressive symptoms. The significance of these results was maintained after correction for confounders, including corticosteroid treatment. Additionally, both groups A and B showed a significant decrease in disease activity in the first 2.5 years after start of treatment and also thereafter. Anti-TNF and IM treatment were associated with a similarly significant decrease in anxiety and depressive symptoms over an observation period of up to 5 years. Conclusion: Besides a clear benefit for disease activity, anti-TNF and IM apparently improve the mood of patients with IBD.

Type of Medium: Online Resource

ISSN: 1756-2848 , 1756-2848

URL: Article

DOI: 10.1177/17562848211033763

Language: English

Publisher: SAGE Publications

Publication Date: 2021

detail.hit.zdb_id: 2440710-0

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