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Autophagy 16‐like 1 rs2241880 G allele is associated with Crohn’s disease in German children
Author(s) -
Lacher Martin,
Schroepf Sebastian,
Ballauff Antje,
Lohse Peter,
Von Schweinitz Dietrich,
Kappler Roland,
Koletzko Sibylle
Publication year - 2009
Publication title -
acta pædiatrica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 115
eISSN - 1651-2227
pISSN - 0803-5253
DOI - 10.1111/j.1651-2227.2009.01438.x
Subject(s) - atg16l1 , nod2 , allele , genotyping , single nucleotide polymorphism , medicine , crohn's disease , pathogenesis , genotype , inflammatory bowel disease , exon , genetics , gene , disease , biology
Aim: Genome‐wide association studies have described an association of the ATG16L1 (autophagy 16‐like 1) gene rs2241880 variant with Crohn’s disease (CD). Therefore, we evaluated this polymorphism in early‐onset CD in 152 children and 253 controls and for the first time determined ATG16L1 colonic expression in German CD children. Methods: Investigation of rs2241880 allele frequencies using a predesigned single nucleotide polymorphism genotyping assay. Analysis of digenic epistasis between rs2241880 and the three common nucleotide‐binding oligomerization domain containing two ( NOD2/CARD15) mutations. Determination of ATG16L1 gene expression in large‐bowel biopsies of selected patients and controls using real‐time polymerase chain reaction. Results: The rs2241880G risk allele frequency was higher in CD compared with controls (63.0% vs. 47.4%; p = 0.0002). No epistasis between NOD2/CARD15 mutations and rs2241880 was observed; however, carriers of both variants had significantly increased disease risk. Transcriptional analysis did not reveal over‐ or underexpression of ATG16L1 in CD patients compared with controls. Conclusion: We confirmed the association of CD with ATG16L1 rs2241880 variant in early‐onset CD. As no epistatic interaction with three common NOD2/CARD15 mutations was observed, the p.Thr300Ala substitution is an independent risk factor for paediatric CD and supports the role for autophagy in disease pathogenesis.