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CCR5-Δ32 mutation is strongly associated with primary sclerosing cholangitis

Genes & Immunity volume 5, pages 444–450 (2004)Cite this article

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-Δ32 is a 32-bp deletion associated with significant reduction in cell surface expression of the receptor. We investigated the role of CCR5-Δ32 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-Δ32 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-Δ32 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-Δ32 mutation may influence disease susceptibility and severity in patients with PSC.

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Acknowledgements

Dr Eri was funded by a research grant from the Queensland Cancer Fund (2000–2002). The Brisbane IBD Research Group's database is supported by an educational grant from Pfizer Australia.

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Authors and Affiliations

  1. Brisbane IBD Research Group, Clinical Research Centre, Royal Brisbane Hospital Research Foundation, Brisbane, Australia

    R Eri, T H J Florin & G L Radford-Smith

  2. Southern Division, University of Queensland School of Medicine, Princess Alexandra Hospital, Brisbane, Australia

    J R Jonsson, A D Clouston & E E Powell

  3. Population and Clinical Sciences Division, Queensland Institute of Medical Research, Brisbane, Australia

    N Pandeya & D M Purdie

  4. Queensland Institute of Medical Research, Genetic Epidemiology Unit, Brisbane, Australia

    N Martin & D Duffy

  5. Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia

    E E Powell

  6. Queensland Liver Transplant Service, Brisbane, Brisbane, Australia

    J Fawcett

  7. University of Queensland Department of Medicine, Mater Health Services Adult Hospital, Brisbane, Australia

    T H J Florin

  8. Department of Gastroenterology, Ned Hanlon Building, Royal Brisbane and Women's Hospital, Brisbane, Australia

    G L Radford-Smith

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Correspondence to G L Radford-Smith.

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Eri, R., Jonsson, J., Pandeya, N. et al. CCR5-Δ32 mutation is strongly associated with primary sclerosing cholangitis. Genes Immun 5, 444–450 (2004). https://doi.org/10.1038/sj.gene.6364113

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