Clinical characteristics of Crohn's disease in 72 families
ABSTRACT Familial aggregation argues for genetic susceptibility to Crohn's disease. The aim of this study was to compare the age of onset and the clinical features of Crohn's disease between patients with familial disease and those with sporadic disease and investigate the concordance for disease location and type among relatives with Crohn's disease.
Seventy-two families with 2 (n = 55), 3 (n = 8), 4 (n = 6), and 5 or more (n = 3) affected first-degree relatives were selected for the study. A population of 1377 patients with sporadic nonfamilial Crohn's disease was used for comparison.
Clinical data were obtained from 176 patients with familial Crohn's disease (79 men and 97 women). Median age at onset was younger in familial Crohn's disease than in sporadic cases: 22 vs. 26.5 years (P < 0.01). In familial cases, fewer patients had exclusively colonic involvement and more patients had both small bowel and colonic involvement. Among relatives of families with 2 affected members, 56% were concordant for disease location and 49% for disease type. These percentages reached 83% and 76%, respectively, within families with more than 2 affected members.
Patients with familial Crohn's disease are characterized by an early age at onset with more extensive disease and may represent a homogeneous clinical subgroup with a particularly strong genetic influence.
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- "Geographic variation of IBD provides clues for researchers to investigate possible environmental etiologic factors. Northern France is characterized by a high incidence of CD with a continuous increase over 20 years, especially in adolescents and young adults (Chouraki et al. 2011; Colombel et al. 1996). Using a Bayesian hierarchical model, we recently reported spatial heterogeneity in the incidence of CD with a predominance of the disease in agricultural areas (Declercq et al. 2010). "
ABSTRACT: Geographical variations in Crohn’s Disease incidence have been reported worldwide suggesting putative variations in the distribution of environmental risk factors. A spatial heterogeneity in standardized incidence ratios of Crohn’s Disease was previously detected in northern France. Aims The goals of this study were to highlight significant atypical clusters in terms of incidence using scan statistics methodology and to study the evolution of these clusters during the study period. Subjects and methods From 1990 to 2006, the EPIMAD Registry recorded 6,472 Crohn’s Disease cases distributed in 273 administrative areas of northern France. Detection of clusters used space-time scan statistics adjusted for gender and age of patients. Results Scan statistics provided identification of 18 significant clusters of two types: 14 time-constant clusters and 4 time-varying clusters. Among the fourteen time-constant clusters, 5 clusters of high incidence and 9 clusters of low incidence were detected. Among the four time-varying clusters, 3 clusters of high incidence and 1 cluster of low incidence were identified. Conclusion The existence of time-constant and time-varying clusters suggests that risk factors of Crohn’s Disease are still at work in our region.Journal of Public Health 12/2013; DOI:10.1007/s10389-013-0580-9 · 2.06 Impact Factor
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- "Both CD and UC patients can be subdivided into a number of subgroups based on the course of the disease, clinical markers, and pathology. These differences are to a certain extent genetically determined (Bayless et al. 1996; Bouma et al. 1998, 1999; Colombel et al. 1996). "
ABSTRACT: There is evidence of a disbalance in the inflammatory regulation of patients with inflammatory bowel diseases (IBD). Interleukin-1 beta plays an important role in the pro-inflammatory response. Our aim was to study the influence which IL1B gene polymorphisms may have on the severity and course of these diseases. Ninety-six patients with ulcerative colitis (UC), 98 patients with Crohn's disease (CD), and 132 ethnically matched healty individuals (HC) were typed for the polymorphic sites in the promoter region (position -511) and in exon 5 (position +3953) of the IL1B gene, using polymerase chain reaction (PCR)-based methods. In the CD group a significant association (P = 0.009) was found in this pair of genes. Homozygotes for allele 1 at position +3953 were more often present (69% vs 31%) in the subgroup of patients carrying at least one copy of allele 2 at position -511. This association was significant in patients with non-perforating disease (P = 0.002), but was not present in patients with perforating-fistulizing disease. The distribution of both allelic pairs in the non-fistulizing group proved to be significantly different from HC (P < 0.05), UC (P < 0.03), and the fistulizing group (P < 0.05). There was a similar association in non-operated patients (P = 0.024), whereas no such association was found in surgically treated patients. Among carriers of allele 2 at position -511, UC patients with more severe bleeding symptoms (P = 0.006) were less frequently found. These results suggest that IL1B gene polymorphisms participate in determining the course and severity of inflammatory bowel disease and contribute to explain the heterogeneity of these diseases.Immunogenetics 07/1999; 49(6):527-31. DOI:10.1007/s002510050530 · 2.49 Impact Factor
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- "The disease incidence peaks in early adulthood and is rising worldwide , with a current prevalence of ∼1/1,000 in Western countries (Probert et al. 1996; Shivananda et al. 1996). Although the cause of IBD is unknown, a strong genetic susceptibility for IBD is shown by both consistent familial clustering of disease (Mayberry 1989; Orholm et al. 1991; Colombel et al. 1996; Satsangi et al. 1996a) and increased concordance in monozygotic twins (Tysk et al. 1988; Thompson et al. 1996). Significant prevalence differences exist among different ethnic groups living in the same geographic region, displayed by the twoto eightfold higher prevalence in Ashkenazi Jews versus non-Jews (Roth et al. 1989). "
ABSTRACT: Inflammatory bowel disease (IBD) is characterized by a chronic relapsing intestinal inflammation, typically starting in early adulthood. IBD is subdivided into two subtypes, on the basis of clinical and histologic features: Crohn disease and ulcerative colitis (UC). Previous genomewide searches identified regions harboring susceptibility loci on chromosomes 1, 3, 4, 7, 12, and 16. To expand our understanding of the genetic risk profile, we performed a 9-cM genomewide search for susceptibility loci in 268 families containing 353 affected sibling pairs. Previous linkages on chromosomes 12 and 16 were replicated, and the chromosome 4 linkage was extended in this sample. New suggestive evidence for autosomal linkages was observed on chromosomes 1, 6, 10, and 22, with LOD scores of 2.08, 2.07, 2.30, and 1.52, respectively. A maximum LOD score of 1.76 was observed on the X chromosome, for UC, which is consistent with the clinical association of IBD with Ullrich-Turner syndrome. The linkage finding on chromosome 6p is of interest, given the possible contribution of human leukocyte antigen and tumor necrosis-factor genes in IBD. This genomewide linkage scan, done with a large family cohort, has confirmed three previous IBD linkages and has provided evidence for five additional regions that may harbor IBD predisposition genes.The American Journal of Human Genetics 04/1999; 64(3):808-16. DOI:10.1086/302294 · 10.99 Impact Factor