Association of NOD2 (CARD 15) genotype with clinical course of Crohn's disease: a cohort study

NOD2/CARD15, TLR4 and CD14 mutations in Scottish and Irish Crohn's disease patients: evidence for genetic heterogeneity within Europe?

“…We have confirmed the associations with early-onset disease 12,23 and ileal disease distribution. 9-12,22,23, 25 The latter observation is strongest in patients with two variant alleles, consistent with the data of Lesage et al 12 We have also seen a relatively weak association with perforating disease at diagnosis, but could not confirm the association with fibrostenosing disease. 8 We observed an association with IBD-associated peripheral arthritis; however, significance was not achieved following correction for multiple variables.…”

“…Lesage et al 12 suggested that patients carrying two variant copies of the CARD15/NOD2 gene are at increased risk of ileal involvement, early age at diagnosis and fibrostenotic behaviour of disease. Ahmad et al, 11 Cuthbert et al, 10 and others 9,19,22,25 have also suggested that carriage of allelic variants is associated with ileal involvement in CD. However, as further data emerge, the primary genotype-phenotype relationship remains controversial and most limited by the quality of phenotypic data.…”

“…The Irish CD group comprised 113 patients (77 females and 36 males) with a median age at diagnosis of 27.5 years (IQR [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. This corresponded to 38 patients diagnosed before the age of 40 years (A1) and 21 diagnosed after the age of 40 years (A2).…”

“…16,17 Most recent data from Ireland and Northern Europe report relatively low allelic frequencies in healthy controls and CD patients (Table 1) and raise the possibility of heterogeneity within European populations of distinct ancestry. [22][23][24][25] Further controversy has arisen in attempts to relate NOD2/CARD15 genotype to phenotype and studies have been confounded the validity of subclassifications used. 27 The age at diagnosis, location of disease and disease behaviour have been adopted in the Vienna classification, 28 and data have emerged to suggest that this clinical classification bears further examination.…”

Detailed assessment of NOD2/CARD15 exonic variation in inflammatory bowel disease in Scotland: implications for disease pathogenesis

“…8 Within Caucasian populations the contribution of these three mutations to disease susceptibility varies markedly with a significantly lower contribution in Northern European 9-15 compared to Southern European populations. 6,13,[16][17][18] In the era of genome-wide association studies, NOD2/CARD15 has been identified at the genome-wide significance level in most populations studied. 3 The contribution of the three common NOD2/CARD15 mutations to disease susceptibility in the Scottish paediatric population is modest, with a population attributable risk (PAR) lower than in most other populations studied at 8%.…”