There is no increased risk of CD for individuals carrying only a single copy of these NOD2/ CARD15 variants, whereas individuals carrying two copies have a 5-15-fold increased risk.
Univariate analysis showed that CD-associated NOD2 variants were significantly associated with fibrostenosing disease in each cohort (P = 0.049 and P = 0.002, respectively).
Thus, NOD2 mediates the host response to bacterial muropeptides derived from peptidoglycan, an activity that is important for protection against Crohn's disease.
These findings suggest that genetic variants at the 5q31 (IBD5) locus may hasten the onset of Crohn disease and cooperate with CARD15 in disease causation.
Together, studies on Nod2 (Card15) provide a conceptual link between inflammatory disorders, such as Crohn's disease and Blau syndrome, and bacterial sensing.
In a Spanish population from Madrid, mutations of the NOD2/CARD15 gene were a marker of susceptibility to Crohn disease and were associated with ileal disease.
In this review, we summarize current information on the genetics of IBD, emphasizing the discovery of CARD15 variants as susceptibility alleles for Crohn's disease and the impact of this discovery on patient care and in delineating pathogenesis of this complex disease.
After excluding the influence of the three DPMs, significant linkage of IBD1 to CD in Jews remained with two peaks at D16S403 (mean allele sharing [MAS] = 0.70] and D16S411 (MAS = 0.59).
While the three risk alleles influence susceptibility to Crohn's disease in Australia, we show that these alleles do not fully explain the linkage evidence and suggest that there are very likely additional IBD1 susceptibility alleles yet to be described in Australian CD at the NOD2 locus.
Sixty-five percent of their genomic DNA samples harbored at least one of six mutations within the CARD15 gene, which previously has been identified as being associated with Crohn disease.
The aim of this study was to determine the significance of the NOD2/CARD15 mutations in Jewish CD patients in Israel, and more specifically, to compare the significance of the mutations to the expression of CD in the Ashkenazi and Sephardic Jewish populations.
In comparison to controls the A allele and the AA genotype frequencies of the single nucleotide polymorphisms in the 3'-UTR were significantly increased only in Crohn's disease patients without a variation in the CARD15 gene.
A positive association between the HLA-DRB1*0103 allele and CD was detected in non-Jewish, familial cases (p = 0.0002), with risk for CD increased by 6.7 fold by the presence of an HLA-DRB1*0103 allele as compared to 1.9 fold and 19 fold by a single or two CARD15 variant alleles, respectively.
Frequency of NOD2/CARD15 variants in both sporadic and familial cases of Crohn's disease across Italy. An Italian Group for Inflammatory Bowel Disease Study.