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  • Title: No major effect of the CD28/CTLA4/ICOS gene region on susceptibility to primary sclerosing cholangitis.
    Author: Wiencke K, Boberg KM, Donaldson P, Harbo H, Ling V, Schrumpf E, Spurkland A.
    Journal: Scand J Gastroenterol; 2006 May; 41(5):586-91. PubMed ID: 16638702.
    Abstract:
    OBJECTIVE: Primary sclerosing cholangitis (PSC) is currently thought to be an immune-mediated disease, where both host genes and environmental factors interact. Some of the immunoregulatory genes responsible for individual susceptibility to PSC have been identified. The co-stimulatory receptor gene cluster on chromosome 2q33 encodes both the positive T-cell regulators CD28 and ICOS, and the negative regulator CTLA4. The CTLA4 gene has been implicated in several immune-mediated diseases, but it is not known whether PSC is associated with any of these genes. MATERIAL AND METHODS: Polymerase chain reaction (PCR)-based genotyping was performed on 144 PSC patients and 285 controls. Two single nucleotide polymorphisms (SNPs) in the CTLA4 gene were investigated as well as six microsatellites covering approximately 262 kb of the flanking regions, including the ICOS and CD28 genes. RESULTS: Overall, there were no statistically significant differences between PSC patients and controls in genotype and allele frequencies for the CTLA4 +49AG and CT60 SNPs or for the CD28-A, CD28-B, SARA43, SARA1, SARA31, and SARA47 microsatellite markers. Nor were any associations with clinical subgroups observed. CONCLUSIONS: There are no major effects of the CD28/CTLA4/ICOS gene region on susceptibility to PSC, but minor contributions (OR <1.8) cannot be excluded.
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