Genotyping of CARD15/NOD2, ATG16L1 and IL23R Genes in Polish Crohn’s Disease (CD) Patients – Are They Related to the Localization of the Disease and Extra-Intestinal Symptoms? (original) (raw)
Related papers
Genetic and environmental factors in the inflammatory bowel disease: A study cases-controls
Gastroenterology, 2000
The inflammatory bowel disease (IBD) follows distinct patterns. Norther countries have the highest rates of the disease.by contrast countries in southern Europe have lower incidence rates. Howewer, it appears that, in Europe, southern countries are "catching up" to their northern neighbors. Aim:a) to analyze the IBD evolutive trend in our sanitary area (Sagunto-.Spain), and b) to confirm the existence of northern and southern differences.. Methods:We performed a prospective and descriptive study of population, that covered the time included between the years 1990-98.AII the cases were detected, working the Hospital of Sagunto (123,000 persons) a center of reference.AlI the cases complied the diagnostic criteria of Lennard-Jones. We calculated the crude rates of incidence (CRI) and the truncated rate incidences for the population group between 15-64y in addition to the rate incidence adjusted (RIA) to the standard european population. Finally, we realized a tendency analysis of the respective incidence rates by method of simple regression, comparing the results of this period with results of a previous work that was realized in the same area (1983-1989). Results: I 15 patients were diagnosticated (72 ulcerative colitis,UC; 39 Crohn's disease,CD; and 4 indeterminate colitis). The results of CRI and RIA are expresed in the Table. If we compare the incidence between the two time periods,we observe a significative increase of UC incidence (6,52 vs 4,08 casesll 05 persons/y) and in global IBD too (l0,43 vs 7,15 cases/f O' persons/y), but not in CD (3,55 vs 3,01 cases/In" persons/y). The prevalence at the end of the study has been 63,30, 52,56 and 121,06 cases per 105 population for UC, CD and the global of IBD, respectively. Conclusions: IBD and UC particularly, is an illness of high incidence in Sagunto (Spain), with a clear increase tendence. We are attending at a progresssive reduction of nothernlsouthern difference, more obvious in CD.
Inflammatory Bowel Diseases, 2007
The aetiology of inflammatory bowel disease (IBD) is unknown, but it has become evident that genetic factors are involved in disease susceptibility. Studies have suggested a north-south gradient in the incidence of IBD, raising the question whether this difference is caused by genetic heterogeneity. We aimed to investigate the prevalence of polymorphisms in CARD15 and TLR4 and occurrence of anti-Saccharomyces cerevisiae (ASCA) and antineutrophil cytoplasmic antibodies (pANCA) in a European population-based IBD cohort.
Artificial Intelligence in Medicine, 2009
Motivations: A large number of single nucleotide polymorphisms (SNPs) are supposed to be involved in onset, differentiation and development of complex diseases. Univariate analysis is limited in studying complex traits since does not take into account gene-gene interaction, and the correlation of multiple SNPs with a specific phenotype. Moreover it might underestimate gene variants with weaker genetic contribution. Therefore more sophisticated techniques should be adopted when investigating the role of a panel of genetic markers in disease predisposition. Methods: In this paper we describe a general method to simultaneously investigate the association between SNPs profile and Crohn's disease (CD), by evaluating the susceptibility or protective role of single or groups of markers. As an association measure we adopted a weighted linear combination of SNPs in which suitable weighting vectors belonged to predefined and over-complete vocabularies of vectors (frames), or were determined by the data. Results: The proposed method found a weighted linear combination of SNPs statistically associated to CD ð p ¼ 3:81 Â 10 À10 Þ describing the role of the markers in the pathology. In particular, MCP1-A2518G gave the major contribution as protective locus, similarly to TNF-aÀC857T, DLG5 rs124869, PTPN22 C1858T variants. The NFkB À94ATTG variants was found to be irrelevant for CD. For the remaining markers, a susceptibility role was attributed also confirming that markers on CARD15 gene, in particular G908R and L1007fsinsC, are involved with CD to the same extent as FcGIIIA
Inflammatory Bowel Diseases, 2011
Background: The role of the IBD5 locus in development of Crohn's disease (CD) has not been clarified. In the Czech population we examined its genetic association using variants of the SLC22A4 (rs1050152), SLC22A5 (rs2631367), two single nucleotide polymorphisms (SNPs) shown to be associated with CD in genomewide studies (rs6596075 and rs2188962), and four SNPs previously shown to tag the haplotype blocks 4, 7, 9, 10 of the IBD5 locus (IGR2063b_1, IGR2230a_1, IGR100Xa_1, IGR3236a_1).
Digestive and Liver Disease, 2004
Background and aims. Both genetic and microbial factors seem to play a pivotal role in the aetiopathogenesis of Crohn's disease. The CARD15 frameshift mutation might link host genetic factors and the indigenous microbial flora, since CARD15 expression is stimulated by peptidoglycan, thereby activating NF-B. It is hypothesised that CARD15 mutation carriers have defective anti-microbial reactions, resulting in more penetrating lesions and antibody responses, which are now being used as highly specific markers for Crohn's disease. The serological marker anti-Saccharomyces cerevisiae antibody directed against cell wall oligomannosidic epitopes has high specificity for Crohn's disease. Perinuclear anti-neutrophil cytoplasmic antibodies have been found in a subgroup of Crohn's disease patients, mostly with colonic involvement. Methods. We investigated the incidence of two CARD15 mutations (3020insC and 2722G > C), anti-S. cerevisiae antibody, and perinuclear anti-neutrophil cytoplasmic antibody in 108 (73F/35M) patients with Crohn's disease with a mean duration of disease since diagnosis of 16 (1-41) years in relation to their phenotype, according to the Vienna classification. Results. The prevalence of CARD15 frameshift mutation was 21%. Of all patients, 62% were anti-S. cerevisiae antibody positive, and 9% had perinuclear anti-neutrophil cytoplasmic antibodies. The prevalence of both anti-S. cerevisiae antibodies and perinuclear anti-neutrophil cytoplasmic antibodies was higher in the mutation carriers compared to non-carriers. Remarkably, all patients with a CARD15 mutation and positive anti-S. cerevisiae antibody had ileal disease. Carriership of the mutation was significantly associated with penetrating behaviour of the disease and weakly associated with stricturing behaviour. Furthermore, anti-S. cerevisiae antibody was associated with ileal disease involvement. Finally, most perinuclear anti-neutrophil cytoplasmic antibody positive patients showed ulcerative-like behaviour of disease (by means of colonic localisation). Conclusions. Genetic and serologic markers might be useful in defining patient subgroups. This may result in a more accurate prediction of disease behaviour, prognosis and therapeutic approach.
European Journal of Gastroenterology & Hepatology, 2006
Background Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with variations in localization and behaviour. Mutations in the NOD2/CARD15 gene on chromosome 16q have been implicated in the pathogenesis of the disease and three main sequence variants, all single nucleotide polymorphisms (SNPs), have been identified in North American and European populations. Aims and methods As no data exist in the Croatian population, we consecutively collected a cohort of 136 CD patients and 91 healthy controls to determine the prevalence of NOD2/CARD15 mutations and their association with phenotypic expression of the disease. All patients and controls were genotyped for Arg702Trp (Hugot SNP8), Gly908Arg (Hugot SNP12), and Leu1007fsinsC (Hugot SNP13) and allele frequencies were compared between the Crohn's patients and controls. The correlation of NOD2/CARD15 genotypes with the phenotypic expression of Crohn's disease was further assessed by logistic regression analysis. Results NOD2/CARD15 variants were found in 38/136 CD patients (27.9%) compared to 10/91 (10.9%) healthy controls (P = 0.0022). Allele frequencies in patients with CD were 13.97%, 4.4% and 11.76%, respectively, for SNP8, 12 and 13, compared to 5.49%, 1.12% and 4.40% in controls (P = 0.041, P = 0.162, P = 0.055). Six CD patients carried double mutations and, remarkably, we identified two homozygous mutants amongst the healthy control group. Surgery over the course of the disease and a younger age at onset of the disease were significantly more frequent in patients who were carriers of NOD2/CARD15 mutations. Conclusions This report on NOD2/CARD15 mutations in Croatian patients with CD demonstrates that this gene is also implicated in susceptibility to CD in the Croatian population. Phenotypic association showed a younger age at diagnosis and a higher need for surgery in patients carrying NOD2/CARD15 mutations. However, the prevalence is somewhat lower compared to other reports, likely due to a more prominent colonic inflammation.
BMC Medical Genetics, 2011
Background: Crohn's disease (CD) has the highest prevalence among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Caucasian populations (NJ). We evaluated a set of well-established CD-susceptibility variants to determine if they can explain the increased CD risk in the AJ population. Methods: We recruited 369 AJ CD patients and 503 AJ controls, genotyped 22 single nucleotide polymorphisms (SNPs) at or near 10 CD-associated genes, NOD2, IL23R, IRGM, ATG16L1, PTGER4, NKX2-3, IL12B, PTPN2, TNFSF15 and STAT3, and assessed their association with CD status. We generated genetic scores based on the risk allele count alone and the risk allele count weighed by the effect size, and evaluated their predictive value. Results: Three NOD2 SNPs, two IL23R SNPs, and one SNP each at IRGM and PTGER4 were independently associated with CD risk. Carriage of 7 or more copies of these risk alleles or the weighted genetic risk score of 7 or greater correctly classified 92% (allelic count score) and 83% (weighted score) of the controls; however, only 29% and 47% of the cases were identified as having the disease, respectively. This cutoff was associated with a >4-fold increased disease risk (p < 10e-16). Conclusions: CD-associated genetic risks were similar to those reported in NJ population and are unlikely to explain the excess prevalence of the disease in AJ individuals. These results support the existence of novel, yet unidentified, genetic variants unique to this population. Understanding of ethnic and racial differences in disease susceptibility may help unravel the pathogenesis of CD leading to new personalized diagnostic and therapeutic approaches.