Autophagy 16-like 1 rs2241880 G allele is associated with Crohn's disease in German children.
Acta Paediatr
; 98(11): 1835-40, 2009 Nov.
Article
em En
| MEDLINE
| ID: mdl-19659808
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Doença de Crohn
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Predisposição Genética para Doença
/
Frequência do Gene
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
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Child
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Child, preschool
/
Female
/
Humans
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Infant
/
Male
País/Região como assunto:
Europa
Idioma:
En
Revista:
Acta Paediatr
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Alemanha