Contribution of the NOD1/CARD4 insertion/deletion polymorphism +32656 to inflammatory bowel disease in Northern Europe.
Inflamm Bowel Dis
; 13(7): 882-9, 2007 Jul.
Article
in En
| MEDLINE
| ID: mdl-17285593
ABSTRACT
BACKGROUND:
NOD1/CARD4 and NOD2/CARD15 are both intracellular pattern-recognition receptors. The NOD1/CARD4 gene lies within a previously described inflammatory bowel disease (IBD) locus (7p14). An association has been suggested between the NOD1/CARD4+32656 deletion*1 variant of a complex deletion*1/insertion*2 polymorphism and IBD in 1 recent study in Europe. Our aim was to assess the influence of NOD1/CARD4+32656 on disease susceptibility and phenotype in the Scottish and Swedish IBD populations.METHODS:
A total of 3,962 individuals (1,791 IBD patients, 522 parents, 1,649 healthy controls) from 2 independent populations (Scotland and Sweden) were genotyped for NOD1/CARD4+32656 A/C by TaqMan and direct sequencing. Case-control, Transmission Disequilibrium Testing (TDT) and detailed genotype-phenotype (Montreal) analyses were performed. The case-control analysis had 80% power to detect an effect size of odds ratio (OR) 1.21 for IBD.RESULTS:
In case-control analyses in Scottish and Swedish patients, none of the genotypes studied in IBD, Crohn's disease (CD) or ulcerative colitis (UC), differed significantly from controls (deletion*1 allelic frequency 73.9%, 73.6%, 73.9%, and 73.6%, respectively all P > 0.8). No epistatic interaction with NOD2/CARD15 was seen for CD susceptibility. TDT analysis in our Scottish early onset cohort was negative.CONCLUSIONS:
This variant allele of NOD1/CARD4+32656 is not associated with a strong effect on susceptibility to IBD in children and adults in Northern Europe. A gene-wide haplotype-based approach may be preferable to analysis of individual variants to assess the contribution of the NOD1/CARD4 gene to IBD.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Inflammatory Bowel Diseases
/
Genetic Predisposition to Disease
/
Nod1 Signaling Adaptor Protein
/
Mutation
Type of study:
Clinical_trials
/
Observational_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
En
Journal:
Inflamm Bowel Dis
Journal subject:
GASTROENTEROLOGIA
Year:
2007
Document type:
Article
Affiliation country:
Reino Unido