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Complex insertion/deletion polymorphism in NOD1 (CARD4) is not associated with inflammatory bowel disease
Mark Tremelling1, Laura Hancock, Francesca Bredin
1IBD Research Group, Addenbrooke's Hospital, University of Cambridge, United Kingdom.
Background And Aims:
Genetic association between inflammatory bowel disease (IBD) and NOD1 (CARD4) has recently been reported. This gene has structural similarity to NOD2 (CARD15), a confirmed susceptibility gene for Crohn"s disease (CD). The NOD1 association was strongest at novel complex indel ND1 + 32656. Our aim was to ascertain the contribution of ND1 + 32656 variants to IBD in a large independent United Kingdom dataset and to identify any subphenotype association within CD and ulcerative colitis (UC).
Methods:
The presence of the ND1 + 32656 variant in our panel was confirmed by direct resequencing in 96 cases. One thousand three hundred seventy unrelated white IBD subjects (671UC, 645 CD, 54 indeterminate) and 760 regionally matched controls were then genotyped for the ND1 + 32656 variant. Data were analyzed by logistic regression methods within STATA software.
Results:
There was no association between ND1 + 32656 and IBD in our panel. There was no heterogeneity between UC and CD, nor within the CD subgroup when conditioned by subphenotype or the presence of NOD2 variants.
Conclusions:
There was no overall evidence of association between IBD and the reported NOD1 susceptibility variant ND1 + 32656 in our panel. The discrepancy with the earlier report may reflect a smaller effect size than previously predicted, a false-positive result in the index study, or population heterogeneity.
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