期刊
INFLAMMATORY BOWEL DISEASES
卷 13, 期 8, 页码 941-946出版社
OXFORD UNIV PRESS INC
DOI: 10.1002/ibd.20162
关键词
Crohn's disease; ulcerative colitis; ATG16L1; CARD15; interaction
资金
- Wellcome Trust Funding Source: Medline
Background: A German genome-wide nonsynonymous single nucleotide polymorphism (nsSNP) association study identified ATG16L1 as a Crohn's disease (CD) susceptibility gene. The association appeared to be confined to the nsSNP rs2241880 and was confirmed in 2 German independent case-control collections (combined P = 4.0 X 10(-8), odds ratio [OR] 1.45; 95% confidence interval [CI]: 1.21-1.74), a CID transmission disequilibrium test (TDT) collection, and an independent UK cohort. A weak statistical interaction with CARD15 was demonstrated. No association with ulcerative colitis (UC) was demonstrated. The aims of the study were to replicate the association with CD, examine subphenotype associations and statistical interactions with CARD15, IL23R, and the IBD5 risk haplotype, as well as explore the association with UC. Methods: The study included 645 CD and 676 UC rigorously phenotyped patients recruited from a single UK center. Unaffected controls comprised either spouses of patients (141) or individuals recruited from well-person clinics (1049). The nsSNP rs2241880 was genotyped using MassArray (Sequenom). Results: A strong association with CD was demonstrated (P = 2.33 X 10(-7), OR 1.45 [1.25-1.67]), but no significant association was demonstrated with any subphenotype. We failed to replicate the reported interaction between rs2241880 and the CARD15 low-risk haplotypes dd and Dd. No significant statistical interaction with the 3 known CD susceptibility genes was seen. No association with UC susceptibility (P = 0.37, OR 1.06 [0.93-1.22]), or any UC subphenotype was identified. Conclusions: We confirmed the findings that ATG16LI is a CD susceptibility gene and found no evidence of interaction with CARD15, IL23R, or IBD5.
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