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- Title
CCR5-Delta32 mutation is strongly associated with primary sclerosing cholangitis.
- Authors
Eri, R; Jonsson, J R; Pandeya, N; Purdie, D M; Clouston, A D; Martin, N; Duffy, D; Powell, E E; Fawcett, J; Florin, T H J; Radford-Smith, G L
- Abstract
CCR5 plays a key role in the distribution of CD45RO+ T cells and contributes to generation of a T helper 1 immune response. CCR5-Delta32 is a 32-bp deletion associated with significant reduction in cell surface expression of the receptor. We investigated the role of CCR5-Delta32 on susceptibility to ulcerative colitis (UC), Crohn's disease (CD) and primary sclerosing cholangitis (PSC). Genotype and allelic association analyses were performed in 162 patients with UC, 131 with CD, 71 with PSC and 419 matched controls. There was a significant difference in CCR5 genotype (OR 2.27, P=0.003) between patients with sclerosing cholangitis and controls. Similarly, CCR5-Delta32 allele frequency was significantly higher in sclerosing cholangitis (17.6%) compared to controls (9.9%, OR 2.47, P=0.007) and inflammatory bowel disease patients without sclerosing cholangitis (11.3%, OR 1.9, P=0.027). There were no significant differences in CCR5 genotype or allele frequency between those with either UC or CD and controls. Genotypes with the CCR5-Delta32 variant were increased in patients with severe liver disease defined by portal hypertension and/or transplantation (45%) compared to those with mild liver disease (21%, OR 3.17, P=0.03). The CCR5-Delta32 mutation may influence disease susceptibility and severity in patients with PSC.
- Publication
Genes and immunity, 2004, Vol 5, Issue 6, p444
- ISSN
1466-4879
- Publication type
Journal Article
- DOI
10.1038/sj.gene.6364113