Autophagy gene ATG16L1 influences susceptibility and disease location but not childhood-onset in Crohn's disease in northern Europe

被引：50

作者：

Van Limbergen, J. ^{[1
,2
]}

Russell, R. K. ^{[3
]}

Nimmo, Er. ^{[1
]}

Drummond, H. E. ^{[1
]}

Smith, L. ^{[1
]}

Anderson, N. H. ^{[1
]}

Davies, G. ^{[1
]}

Gillett, P. M. ^{[2
]}

McGrogon, P. ^{[3
]}

Weaver, L. T. ^{[4
]}

Bisset, W. M. ^{[5
]}

Mahdi, G. ^{[5
]}

Arnott, I. D. ^{[1
]}

Wilson, D. C. ^{[1
,2
]}

Satsangi, J. ^{[1
]}

机构：

[1] Univ Edinburgh, Western Gen Hosp, Gastroenterol Unit, Mol Med Ctr, Edinburgh EH4 2XU, Midlothian, Scotland

[2] Royal Hosp Sick Children, Dept Pediat Gastroenterol & Nutr, Edinburgh EH9 1LF, Midlothian, Scotland

[3] Yorkhill Hosp, Dept Paediat Gastroenterol, Glasgow, Lanark, Scotland

[4] Univ Glasgow, Dept Child Hlth, Glasgow, Lanark, Scotland

[5] Royal Aberdeen Childrens Hosp, Dept Paediat Gastroenterol, Aberdeen, Scotland

来源：

INFLAMMATORY BOWEL DISEASES | 2008年 / 14卷 / 03期

基金：

英国惠康基金;

关键词：

ATG16L1; autophagy; Crohn's disease; inflammatory bowel disease; genetics; pediatrics;

D O I：

10.1002/ibd.20340

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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 1131) 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.

引用

页码：338 / 346

页数：9

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