Ulcerative Colitis: Schrumpf E

Karlsen TH, Boberg KM, Vatn M, Bergquist A, Hampe J, Schrumpf E, Thorsby E, Schreiber S, Lie BA, Anonymous00129. · Medical Department, Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, Oslo, Norway. · Genes Immun. · Pubmed #17301827 No free full text.

Abstract: Approximately 80% of patients with primary sclerosing cholangitis (PSC) of Northern European origin have inflammatory bowel disease (IBD), the majority ulcerative colitis (UC). An inherent problem in interpreting positive findings in genetic association studies of PSC is thus to distinguish between factors associated with hepatobiliary versus intestinal pathology. We aimed to clarify to what extent human leukocyte antigen (HLA) class II associations in UC patients with and without PSC differ. High-resolution DRB1 and DQB1 typing was performed in 365 Scandinavian PSC patients, an independent cohort of 330 Norwegian UC patients and 368 healthy controls. HLA associations found in PSC were mostly distinct from those seen in UC, and no significant differences were noted between PSC patients with concurrent UC and PSC patients without IBD. This suggests different HLA associated genetic susceptibility to PSC and UC, and supports notions that UC in PSC may represent a distinct UC phenotype.

Karlsen TH, Hampe J, Wiencke K, Schrumpf E, Thorsby E, Lie BA, Broomé U, Schreiber S, Boberg KM. · Medical Department, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. · Am J Gastroenterol. · Pubmed #17100974 No free full text.

Abstract: OBJECTIVES: Approximately 80% of patients with primary sclerosing cholangitis (PSC) of Northern European origin have concurrent inflammatory bowel disease (IBD). The majority have ulcerative colitis, but there is also an association with Crohn's colitis. The pathogenetic link between PSC and IBD is unknown. We aimed to assess whether genetic risk factors in PSC can be identified on the basis of known IBD susceptibility genes and the shared PSC-IBD phenotype. METHODS: IBD-associated polymorphisms in the CARD15, TLR-4, CARD4, SLC22A4, SLC22A5, DLG5, and MDR1 genes were genotyped in a large cohort of 365 Scandinavian PSC patients and 368 healthy controls using TaqMan technology. RESULTS: No significant association between any of the investigated genetic IBD risk variants and overall susceptibility to PSC was observed. Apart from a tendency toward an increased carrier frequency of the mutant CARD15 alleles in PSC patients with concurrent Crohn's disease as compared with healthy controls (15.6%vs 9.0%, P = 0.22), no association with any of the polymorphisms investigated was evident even when considering only PSC patients with concurrent IBD. CONCLUSION: It seems unlikely that IBD-associated polymorphisms in the CARD15, TLR-4, CARD4, SLC22A4, SLC22A5, DLG5, and MDR1 genes confer susceptibility to PSC. The current knowledge of genetic risk factors in IBD may not contribute to our understanding of molecular mechanisms involved in the pathogenesis of PSC or the IBD phenotype in PSC.

Bowlus CL, Karlsen TH, Broomé U, Thorsby E, Vatn M, Schrumpf E, Lie BA, Boberg KM. · Division of Gastroenterology, University of California Davis Medical Center, 4150 V Street, PSSB3500, Sacramento, CA 95817, USA. · J Hepatol. · Pubmed #16750586 No free full text.

Abstract: BACKGROUND/AIMS: Mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) has been implicated in the aberrant homing of intestinal lymphocytes to the liver in primary sclerosing cholangitis (PSC). Intercellular adhesion molecule-1 (ICAM-1) has also been implicated in the pathogenesis of PSC and the E/E genotype of the K469E polymorphism has been reported to be associated with PSC susceptibility. The aims of this study were to determine if MAdCAM-1 polymorphisms or the K469E polymorphism of ICAM-1 are associated with PSC in Scandinavia. METHODS: Seven single nucleotide polymorphisms (SNPs) in MAdCAM-1 and the G421R and K469E ICAM-1 SNPs were genotyped in 365 PSC patients from Norway and Sweden. 327 Norwegian ulcerative colitis (UC) patients and 368 Norwegian bone marrow donors served as controls. RESULTS: No significant association with PSC was found for any of the MAdCAM-1 or ICAM-1 SNPs. Allele frequencies for these polymorphisms were not significantly different between PSC patients with UC, UC patients and healthy controls. CONCLUSIONS: Polymorphisms in MAdCAM-1 are not likely to significantly affect PSC susceptibility. In addition, the E/E genotype of the K469E in ICAM-1 does not influence PSC susceptibility in Scandinavia.

Brandsaeter B, Schrumpf E, Clausen OP, Abildgaard A, Hafsahl G, Bjøro K. · Department of Medicine, Rikshospitalet, Oslo, Norway. · Liver Transpl. · Pubmed #15390337 links to  free full text

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Wiencke K, Louka AS, Spurkland A, Vatn M, Schrumpf E, Boberg KM, Anonymous00089. · Institute of Immunology, Rikshospitalet University Hospital, 0027 Oslo, Norway. · J Hepatol. · Pubmed #15288468 No free full text.

Abstract: BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) is considered an immune mediated liver disease of multifactorial and multigenetic aetiology. Concomitant ulcerative colitis (UC) is seen in many PSC patients, but the pathogenetic link between these disorders is unknown. Due to association with inflammation, fibrosis, and cancer development, the matrix metalloproteinases MMP-1 and MMP-3 are candidate genes for predisposition to both PSC, UC and cholangiocarcinoma. METHODS: We investigated the association of MMP-1 and MMP-3 promoter polymorphisms in 165 Norwegian PSC patients compared to 118 UC patients and 346 healthy controls. RESULTS: There were no differences in MMP-1 and MMP-3 frequencies between PSC patients and UC patients or healthy controls. PSC patients with UC showed an increased frequency of the MMP-3 allele 5A compared to PSC patients without UC (60% vs. 45%; P(c)=0.01). All patients (100%) with cholangiocarcinoma carried MMP-1 allele 1G, compared to only 72% of PSC patients without cholangiocarcinoma. CONCLUSIONS: We found no general associations of the MMP-1 and MMP-3 genes to PSC or UC among Norwegian patients, but specific alleles were associated to subsets of PSC patients with UC and cholangiocarcinoma. The results support the theory of genetic heterogeneity among PSC patients.