Wiencke Kristine, Boberg Kirsten Muri, Donaldson Peter, Harbo Hanne, Ling Vincent, Schrumpf Erik, Spurkland Anne
Medical Department, Rikshospitalet University Hospital, Oslo, Norway.
Scand J Gastroenterol. 2006 May;41(5):586-91. doi: 10.1080/00365520500377870.
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.
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.
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.
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.
原发性硬化性胆管炎（PSC）目前被认为是一种免疫介导的疾病，宿主基因和环境因素在其中相互作用。一些导致个体对PSC易感性的免疫调节基因已被确定。位于2q33染色体上的共刺激受体基因簇编码阳性T细胞调节因子CD28和ICOS，以及阴性调节因子CTLA4。CTLA4基因已被认为与多种免疫介导的疾病有关，但尚不清楚PSC是否与这些基因中的任何一个相关。
对144例PSC患者和285例对照进行基于聚合酶链反应（PCR）的基因分型。研究了CTLA4基因中的两个单核苷酸多态性（SNP）以及覆盖侧翼区域约262 kb的六个微卫星，包括ICOS和CD28基因。
总体而言，PSC患者和对照在CTLA4 +49AG和CT60 SNP的基因型和等位基因频率方面，或在CD28-A、CD28-B、SARA43、SARA1、SARA31和SARA47微卫星标记方面，均无统计学上的显著差异。也未观察到与临床亚组的任何关联。
CD28/CTLA4/ICOS基因区域对PSC易感性没有主要影响，但不能排除微小贡献（比值比<1.8）。
