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Genetic Variants of DMBT1 and SFTPD and Disease Severity in Paediatric Inflammatory Bowel Disease-A Polish Population-Based Study.

ABSTRACT: Deleted in malignant brain tumours 1 protein (DMBT1) and surfactant protein D (SFTPD) are antimicrobial peptides previously linked to inflammatory bowel disease (IBD) susceptibility. This study attempts to link the most potential IBD-associated polymorphisms in DMBT1 and SFTPD with the disease severity in children. A total of 406 IBD patients (Crohn's disease (CD) n = 214 and ulcerative colitis (UC) n = 192) were genotyped using hydrolysis probe assay. Clinical expression was described by disease activity scales, albumin and C-reactive protein levels, localisation and behaviour (Paris classification), systemic steroid, immunosuppressive, biological, and surgical treatment, number of exacerbation-caused hospitalisations, relapses and nutritional status. IBD patients with the risk genotype (AA) in DMBT1 rs2981804 had more frequent biological treatment (AA: vs. AG/GG; p = 0.012), concomitant diseases (AA vs. AG vs. GG; p = 0.015) and cutaneous manifestations (AA vs. AG/GG, p = 0.008). In UC, rs2981804 genotypes might be linked with albumin concentrations at diagnosis (AA vs. AG vs. GG; p = 0.009). In CD, DMBT1 rs2981745 was significantly associated with the number of severe relapses per year of disease (p = 0.020) and time-to-immunosuppression (p = 0.045). SFTPD was seemingly found to be associated with age at first immunosuppression in IBD (CC vs. CT vs. TT; p = 0.048). In conclusion, selected polymorphisms of DMBT1 and SFTPD might be associated with some disease severity measures in children with IBD. However, the magnitude of associations and their clinical relevance might be minor.

SUBMITTER: Glapa-Nowak A

PROVIDER: S-EPMC8618964 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: Multiple genes have been implicated by association studies in altering inflammatory bowel disease (IBD) predisposition. Paediatric patients often manifest more extensive disease and a particularly severe disease course. It is likely that genetic predisposition plays a more substantial role in this group. OBJECTIVE: To identify the spectrum of rare and novel variation in known IBD susceptibility genes using exome sequencing analysis in eight individual cases of childhood onset severe disease. DESIGN: DNA samples from the eight patients underwent targeted exome capture and sequencing. Data were processed through an analytical pipeline to align sequence reads, conduct quality checks, and identify and annotate variants where patient sequence differed from the reference sequence. For each patient, the entire complement of rare variation within strongly associated candidate genes was catalogued. RESULTS: Across the panel of 169 known IBD susceptibility genes, approximately 300 variants in 104 genes were found. Excluding splicing and HLA-class variants, 58 variants across 39 of these genes were classified as rare, with an alternative allele frequency of <5%, of which 17 were novel. Only two patients with early onset Crohn's disease exhibited rare deleterious variations within NOD2: the previously described R702W variant was the sole NOD2 variant in one patient, while the second patient also carried the L1007 frameshift insertion. Both patients harboured other potentially damaging mutations in the GSDMB, ERAP2 and SEC16A genes. The two patients severely affected with ulcerative colitis exhibited a distinct profile: both carried potentially detrimental variation in the BACH2 and IL10 genes not seen in other patients. CONCLUSION: For each of the eight individuals studied, all non-synonymous, truncating and frameshift mutations across all known IBD genes were identified. A unique profile of rare and potentially damaging variants was evident for each patient with this complex disease.

Project description:BackgroundThe skin-gut axis, characterized by bidirectional communication between the skin and gut, plays a crucial role in the pathogenesis of psoriasis and inflammatory bowel diseases (IBD).ObjectivesWe aimed to explore the association between psoriasis and IBD and identify predictors associated with IBD development among patients with psoriasis.DesignRetrospective cohort study.MethodsA retrospective study which utilized an electronic database from the Meuhedet Health Maintenance Organization (MHMO) in Israel. Psoriasis was categorized as severe if any systemic agent or phototherapy was administered. Univariate and multivariate logistic regressions were used to identify specific predictors for IBD, with adjustments made for potential confounders. The study received approval from the Ethical Committee of the MHMO.ResultsIn total, 61,003 adult patients who were diagnosed with psoriasis between 2000 and 2022 were included. Among them, 1495/61,003 patients (2.4%) were diagnosed with IBD, as compared to 3834/244,012 patients (1.6%) in the non-psoriasis group [adjusted odds ratio (OR): 1.47; 95% confidence interval (CI): 1.37-1.56; p < 0.001]. Increased age (OR: 1.01; 95% CI: 1.01-1.02; p < 0.001), male gender (OR: 1.22; 95% CI: 1.03-1.45; p = 0.024), and Jewish ethnicity (OR: 2.5; 95% CI: 1.2-4.1; p < 0.001) were identified as significant risk factors for IBD. Spondyloarthropathies, including psoriatic arthritis (OR: 2.27; 95% CI: 1.86-2.77; p < 0.001) and ankylosing spondylitis (OR: 2.82; 95% CI: 1.5-5.32; p < 0.05), were associated with a higher prevalence of IBD. Furthermore, severe psoriasis was significantly associated with a higher likelihood of IBD, compared to mild psoriasis (OR: 16.03; 95% CI: 11.02-23.34; p < 0.001).ConclusionA significant association between psoriasis and IBD was demonstrated, including its subtypes: Crohn's disease and ulcerative colitis. Moreover, such association may depend on psoriasis severity as determined by the treatment used. This association warrants further investigation and implies a potential need for closer monitoring of patients with severe psoriasis.

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Genetic Variants of DMBT1 and SFTPD and Disease Severity in Paediatric Inflammatory Bowel Disease-A Polish Population-Based Study.

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