Association of NOD2 (CARD 15) genotype with clinical course of Crohn's disease: a cohort study (original) (raw)
Related papers
Lack of common NOD2 variants in Japanese patients with Crohn's disease
Gastroenterology, 2002
Background & Aims: Previous studies have linked Crohn's disease (CD) to the pericentromeric region of chromosome 16 (IBD1). Three independent studies of Western populations have recently shown that 3 variants of NOD2, a gene located at 16q12, are associated with susceptibility to CD. Here, we have evaluated the 3 NOD2 variants in Japanese patients to determine whether the gene is also associated with susceptibility to CD in a non-Western population. Methods: Blood samples were obtained from 350 patients with CD, 272 patients with ulcerative colitis, and 292 healthy controls at 3 hospitals in Japan. DNA was sequenced in the region of the 3 NOD2 variants (C2104T in exon 4, G2722C in exon 8, and 3020insC in exon 11) by genomic polymerase chain reaction followed by direct sequencing. Results: Among the subjects in our 3 study groups, including patients with CD, patients with ulcerative colitis, and healthy controls, none had common NOD2 variants that have been associated with CD in white patients. Conclusions: These results indicate that genetic variation, which may predispose some human populations to CD, may not be present in other populations and specifically that common variants in NOD2 found in white patients with CD are not associated with CD in the Japanese population.
Scandinavian Journal of Gastroenterology, 2003
Scand J Gastroenterol Downloaded from informahealthcare.com by Vrije Universiteit Amsterdam on 03/12/12 For personal use only. Review Scand J Gastroenterol Downloaded from informahealthcare.com by Vrije Universiteit Amsterdam on 03/12/12 For personal use only. Scand J Gastroenterol Downloaded from informahealthcare.com by Vrije Universiteit Amsterdam on 03/12/12 For personal use only. Review Scand J Gastroenterol Downloaded from informahealthcare.com by Vrije Universiteit Amsterdam on 03/12/12 For personal use only. 1114 Review Scand J Gastroenterol Downloaded from informahealthcare.com by Vrije Universiteit Amsterdam on 03/12/12
Crohn’s Disease Susceptibility and Onset Are Strongly Related to Three NOD2 Gene Haplotypes
Journal of Clinical Medicine
The genetic background and the determinants influencing the disease form, course, and onset of inflammatory bowel disease (IBD) remain unresolved. We aimed to determine the NOD2 gene haplotypes and their relationship with IBD occurrence, clinical presentation, and onset, analyzing a cohort of 578 patients with IBD, including children, and 888 controls. Imaging or endoscopy with a histopathological confirmation was used to diagnose IBD. Genotyping was performed to assess the differences in genotypic and allelic frequencies. Linkage disequilibrium was analyzed, and associations between haplotypes and clinical data were evaluated. We emphasized the prevalence of risk alleles in all analyzed loci in patients with Crohn disease (CD). Interestingly, c.2722G>C and c.3019_3020insC alleles were also overrepresented in ulcerative colitis (UC). T-C-G-C-insC, T-C-G-T-insC, and T-T-G-T-wt haplotypes were correlated with the late-onset form of CD (OR = 23.01, 5.09, and 17.71, respectively), wh...
Lessons to be learned from the NOD2 gene in Crohn's disease
European Journal of Gastroenterology & Hepatology, 2003
The recent discovery that CARD15/NOD2 is involved in the genetic predisposition to Crohn's disease (CD) provides the final demonstration that CD is a genetic disorder. The gene explains about 20% of the genetic susceptibility. CARD15 mutations are present in 30-50% of CD patients compared to 7-20% of healthy controls. Interestingly, CD patients often carry mutations on their two chromosomes suggesting a mutation dose effect. Unfortunately, even if the association between the three main CARD15 mutations (R702W, G908R and 1007fs) and CD is clearly established, it is not useful today to genotype asymptomatic at risk people or inflammatory bowel disease patients as a routine. More interestingly and for the first time, CARD15 points out a specific pathway involved in CD mechanism. Because CARD15 is able to be activated by components of the bacterial wall and further induce the activation of NFk kB, a proinflammatory molecule, CARD15 discovery makes the link, at the molecular level, between bacteria and inflammation of the digestive tract.
2009
NOD2/CARD15 gene variants may be associated with distinct phenotypic expressions of Crohn's disease, however, this association may change according to the ethnic and regional variation. The aim of this study was to analyze the impact of NOD2/CARD15 gene mutations on disease phenotype in Turkish Crohn's disease patients. Fourty-five Crohn's disease patients (32 males, 13 females) with a mean age of 38.7 ± 12.1 (range: 19-78) were enrolled into this prospective study. The three major polymorphisms (R702W, G908R, 3020insC) on NOD2/CARD15 gene were studied from the peripheral blood genomic DNA. R702W and G908R mutations were studied by PCR-RFLP method, and 3020insC mutation was studied by DNA sequencing. No homozygous mutation was detected. Heterozygous R702W, G908R, and 3020insC mutations were detected in 4, 3, and 4 patients, respectively. The frequency of R702W, G908R, and 3020insC mutations was found to be 4.4, 3.3, and 4.4%, respectively. The overall mutation frequency was found to be 12.2%. There was no statistically difference between the clinical course of the patients with (n = 11) and without (n = 34) mutations (p>0.05). NOD2/CARD15 gene polymorphisms do not have impact on disease phenotype in Turkish Crohn's disease patients.