Linkage and Association between Inflammatory Bowel Disease and a Locus on Chromosome 12

Abstract

Genetic epidemiological studies have shown that genetic factors are important in the pathogenesis of the idiopathic inflammatory bowel diseases (IBD), Crohn disease (CD), and ulcerative colitis (UC). A genome screen in the United Kingdom found linkage of IBD to a 41-cM region of chromosome 12, surrounding D12S83. We aimed to replicate this linkage and to narrow the region of interest. Nonparametric linkage analyses at microsatellites surrounding D12S83 were performed in 122 North American Caucasian families containing 208 genotyped IBD-affected relative pairs. Transmission/disequilibrium tests (TDTs) were also performed. We confirmed that IBD is linked to chromosome 12 (peak GENEHUNTER-PLUS LOD* score 2.76 [P = .00016] between D12S1724 and D12S90). The evidence for linkage is contributed by both the group of CD-affected relative pairs (peak GENEHUNTER-PLUS LOD* score 1.79 [P = .0021] between D12S1724 and D12S90) and the group of UC-affected relative pairs (peak GENEHUNTER-PLUS LOD* score 1.82 [P = .0019] at D12S335). The TDT is positive at the D12S83 locus (global chi2 = 16.41, 6 df, P = .012). In conclusion, we have independently confirmed linkage of IBD to the chromosome 12 region that we investigated. A positive TDT at D12S83 suggests that we have greatly narrowed the chromosome 12 region that contains an IBD locus.

IL-TIF/IL-22: genomic organization and mapping of the human and mouse genes

“…This suggests the presence of a cytokine cluster in this region of the genome, which has been associated with asthma 10,11 and inflammatory bowel disease. 12,13 In the mouse, the corresponding locus is involved in the persistence of Theiler's virus in the central nervous system but a role for the IFN␥ gene has been ruled out, 14 raising the possibility that IL-TIF could play a role in this model. The main biological activities of IL-TIF remain to be identified.…”

Polymorphisms of the vitamin D receptor gene and the risk of inflammatory bowel disease: a meta-analysis

“…VDR-knockout mouse studies showed that loss of VDR expression resulted in perturbed inflammation reactions in the gastrointestinal tract, leading to increased susceptibility to mucosal barrier damage and increased risk of IBD (Froicu et al, 2003;Froicu and Cantorna, 2007;Kong et al, 2008). Meanwhile, the gene encoding VDR is located 3 cM to the microsatellite marker D12S85 on chromosome 12, which has been reportedly linked to UC and CD (Satsangi et al, 1996;Curran et al, 1998;Duerr et al, 1998;Hampe et al, 1999). Therefore, the VDR gene is regarded as a logical functional and positional candidate in susceptibility to IBD.…”

Genetic analysis in Finnish families with inflammatory bowel disease supports linkage to chromosome 3p21

“…13 Linkage to another promising IBD locus (IBD2) on chromosome 12 has been supported by many independent studies, especially in UC families. 2,7,10,11,14 The locus on chromosome 6p referred to as IBD3 locus is not as definitively replicated as the IBD1 and IBD2 loci. 15 ± 17 Linkage to chromosome 1 in American Chaldean population is the only linkage report, so far, from an isolated population, 18 that strengthens and restricts the assignment of the susceptibility locus previously reported in outbred population.…”