Contribution of the NOD1/CARD4 insertion/deletion polymorphism +32656 to inflammatory bowel disease in Northern Europe
✍ Scribed by J. Van Limbergen; R.K. Russell; E.R. Nimmo; L. Törkvist; C.W. Lees; H.E. Drummond; L. Smith; N.H. Anderson; P.M. Gillett; P. McGrogan; K. Hassan; L.T. Weaver; W.M. Bisset; G. Mahdi; I.D. Arnott; U. Sjöqvist; M. Lördal; S.M. Farrington; M.G. Dunlop; D.C. Wilson; J. Satsangi
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 146 KB
- Volume
- 13
- Category
- Article
- ISSN
- 1078-0998
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✦ Synopsis
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.