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  • 2005-2009  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    International journal of immunogenetics 32 (2005), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Nuclear factor κB (NF-κB) designates a group of critical transcription factors involved in a variety of immunologic and/or inflammatory processes. Conceivably, genes involved in the NF-κB pathway make interesting candidate genes for chronic inflammatory disorders, including the inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC). In two mouse models of colitis, strong linkage has been observed with a locus on chromosome 3 that harbours the Nfkb1 gene. In addition, a polymorphism in the promoter region of the human NFKB1 gene was found to be associated with susceptibility to UC. In this study, we searched to confirm this previously found association in IBD in a different population. Allele and genotype frequencies of the −94 ins/delATTG polymorphism were determined in 266 unrelated Dutch Caucasian IBD patients (127 UC, 139 CD), and 155 matched healthy controls. The allele frequency of the deletion was significantly higher in UC patients (P = 0.019), but not in CD patients, compared to healthy controls, and the UC patients homozygous for the −94 ATTG deletion had a younger age of onset. Our findings confirm the previously found association between this polymorphism and susceptibility to UC in an independent study population and adds further evidence for the role of this gene in disease susceptibility.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 22 (2005), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Tioguanine (thioguanine) has been proposed as a rescue thiopurine for azathioprine or mercaptopurine intolerant inflammatory bowel disease patients. The use of tioguanine leads to high 6-tioguaninenucleotide (6-thioguaninenucleotide) levels in red blood cells but, contra-intuitively, these have yet not been associated with an increased risk of myelotoxicity.Aim : To assess the role of 6-tioguaninenucleotide concentrations in developing myelotoxicity during tioguanine treatment.Methods : Database analysis of 25 patients treated with tioguanine. Clinical findings and laboratory parameters were related to 6-tioguaninenucleotide levels.Results : One patient developed a myelodepression (21 mg TG/day for 3 months and 6-tioguaninenucleotide 714 pmol/8 × 108 red blood cells). 6-Tioguaninenucleotide levels varied greatly between individuals (mean 6-tioguaninenucleotide level 621 pmol/8 × 108 red blood cells, s.d. 340 pmol/8 × 108 red blood cells and range 34–1653 pmol/8 × 108 red blood cells). The TG dosages (mean 20.6 mg/day and median 20 mg/day) did not correlate with 6-tioguaninenucleotide levels (r = 0.31, N.S.). High 6-tioguaninenucleotide levels (〉450 pmol/8 × 108 red blood cells) did not effect haemoglobin concentrations (mean 8 mmol/L), peripheral leucocyte (mean 7.5 × 109/L) or platelet counts (mean 298 × 109/L). No correlations were established between laboratory parameters, type of disease and 6-tioguaninenucleotide level.Conclusion : High 6-tioguaninenucleotide levels in erythrocytes (〉450 pmol/8 × 108) during TG treatment compared to azathioprine or mercaptopurine treatment are not indicative for (developing) myelotoxicity.
    Type of Medium: Electronic Resource
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