| Autophagy gene ATG16L1 influences susceptibility and disease location but not childhood-onset in Crohn's disease in Northern Europe. | |
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MedLine Citation:
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PMID: 18088053 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The rs2241880A/G variant of the ATG16L1 gene has been associated with susceptibility to ileal Crohn's disease (CD) in adults. Our aim was to assess whether germline variation of ATG16L1 acts as an independent determinant of susceptibility to childhood-onset CD in the high-incidence Scottish population. METHODS: In all, 2195 subjects (361 children (inflammatory bowel disease [IBD] diagnosis <17 years), their parents (n = 634), 855 adult IBD patients, and 345 controls were genotyped. Case-control analysis was powered to detect effect sizes with an odds ratio (OR) >1.39 in pediatric CD. Case-control analysis, transmission disequilibrium testing (TDT), analysis of variance (ANOVA) of growth parameter z-scores, Kruskal-Wallis test (age at diagnosis), and multifactorial genotype-phenotype analysis (Montreal classification) were performed. 7.8% of pediatric CD patients and 37.2% of adult CD patients had pure ileal disease. RESULTS: We confirmed the association of the rs2241880G-allele with adult-onset CD (60.7% versus controls 53.9%, P = 0.01, OR 1.32, 95% confidence interval [CI] 1.07-1.63) in contrast to childhood-onset CD (54.1% versus controls, P = 0.95, OR 1.01, 95% CI 0.80-1.26). TDT analysis was negative. Genotype-phenotype analysis demonstrated an association of pure ileal disease with the rs2241880G-allele (P = 0.02, OR 1.34, 95% CI 1.03-1.74). Using binary logistic regression analysis we confirmed the effect of rs2241880 genotype (GG) on ileal disease versus colonic disease (P = 0.03, OR 2.43, 95% CI 1.05-5.65). ATG16L1 genotype did not influence age at CD diagnosis. ANOVA of z-scores of height, weight, and body mass index (BMI) at CD diagnosis in children showed no association with genotype. CONCLUSIONS: The ATG16L1 variant is associated with susceptibility to adult CD in Scotland, but not early-onset disease. These contrasting effects are primarily driven by differences in disease location between early-onset and adult-onset disease. |
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Authors:
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J Van Limbergen; R K Russell; E R Nimmo; H E Drummond; L Smith; N H Anderson; G Davies; P M Gillett; P McGrogan; L T Weaver; W M Bisset; G Mahdi; I D Arnott; D C Wilson; J Satsangi |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Inflammatory bowel diseases Volume: 14 ISSN: 1078-0998 ISO Abbreviation: Inflamm. Bowel Dis. Publication Date: 2008 Mar |
Date Detail:
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Created Date: 2008-02-13 Completed Date: 2008-05-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9508162 Medline TA: Inflamm Bowel Dis Country: United States |
Other Details:
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Languages: eng Pagination: 338-46 Citation Subset: IM |
Affiliation:
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Gastrointestinal Unit, Molecular Medicine Centre, Western General Hospital, University of Edinburgh, Crewe Road South, Edinburgh, UK. johanvanlimbergen@hotmail.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Age of Onset Alleles Carrier Proteins / genetics* Case-Control Studies Child Crohn Disease / epidemiology*, genetics* DNA / genetics* Female Gene Frequency Genetic Predisposition to Disease / epidemiology*, genetics Genotype Humans Male Middle Aged Nod2 Signaling Adaptor Protein / genetics Odds Ratio Phenotype Polymorphism, Genetic* Scotland / epidemiology |
| Grant Support | |
ID/Acronym/Agency:
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072789/Z/03/Z//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/ATG16L1 protein, human; 0/Carrier Proteins; 0/NOD2 protein, human; 0/Nod2 Signaling Adaptor Protein; 9007-49-2/DNA |
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