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CC-type chemokine receptor 5-Delta 32 mutation protects against primary sclerosing cholangitis

(2006) INFLAMMATORY BOWEL DISEASES. 12(4). p.272-277
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Abstract
Background: Primary sclerosing cholangitis (PSC) is commonly associated with inflammatory bowel disease (IBD) and characterized by fibrosing inflammatory destruction of biliary ducts. The pathogenesis of PSC remains unknown, but immunological, bacteria], viral, and toxic factors play a role in a genetically susceptible host. We hypothesized that CC-type chemokine receptor 5 (CCR5) would be ail interesting candidate gene for susceptibility to PSC from its chromosomal location within the IBD Susceptibility locus on 3p21, as well as from a functional perspective. We therefore investigated the role of the functional 32-bp deletion in this gene (CCR5-Delta 32) with regard to susceptibility to PSC. Methods: A total of 110 patients with PSC, 56 with concomitant IBD (23 with Crohn's disease, 28 with ulcerative colitis, 5 with indeterminate colitis), were collected. All of the subjects were genotyped for CCR5-Delta 32 with polymerase chain reaction amplification, followed by detection on ethidium bromide-stained agarose gel. Genotypes and allele frequencies were compared with a cohort of IBD patients without PSC (n = 400) and healthy control Subjects (n = 362). Results: The frequency of the CCR5-Delta 32 mutation in PSC (6.8%) was significantly lower compared with IBD (12.6%; P = 0.016) and healthy control subjects (12.2%, P = 0.026), suggesting a protective effect of this mutation on PSC. None of the PSC patients with severe disease necessitating liver transplantation (it = 17) carried CCR5-Delta 32. Conclusions: Because an intact CCR5 receptor is needed for internalization of specific pathogens and homing of memory T lymphocytes to the liver, we hypothesize that a deficient expression of this receptor resulting from the CCR5-Delta 32 variant may protect against PSC.
Keywords
disease susceptibility, sclerosing cholangitis, genetics, INFLAMMATORY-BOWEL-DISEASE, HIV-1 INFECTION, INDIVIDUALS, GENE, HLA, POLYMORPHISM, ASSOCIATION, HAPLOTYPES, CORECEPTOR, RESISTANCE

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Chicago
Henckaerts, L, J Fevery, W Van Steenbergen, C Werslype, P Yap, F Nevens, T Roskams, Louis Libbrecht, P Rutgeerts, and S Vermeire. 2006. “CC-type Chemokine Receptor 5-Delta 32 Mutation Protects Against Primary Sclerosing Cholangitis.” Inflammatory Bowel Diseases 12 (4): 272–277.
APA
Henckaerts, L., Fevery, J., Van Steenbergen, W., Werslype, C., Yap, P., Nevens, F., Roskams, T., et al. (2006). CC-type chemokine receptor 5-Delta 32 mutation protects against primary sclerosing cholangitis. INFLAMMATORY BOWEL DISEASES, 12(4), 272–277.
Vancouver
1.
Henckaerts L, Fevery J, Van Steenbergen W, Werslype C, Yap P, Nevens F, et al. CC-type chemokine receptor 5-Delta 32 mutation protects against primary sclerosing cholangitis. INFLAMMATORY BOWEL DISEASES. 2006;12(4):272–7.
MLA
Henckaerts, L, J Fevery, W Van Steenbergen, et al. “CC-type Chemokine Receptor 5-Delta 32 Mutation Protects Against Primary Sclerosing Cholangitis.” INFLAMMATORY BOWEL DISEASES 12.4 (2006): 272–277. Print.
@article{3183480,
  abstract     = {Background: Primary sclerosing cholangitis (PSC) is commonly associated with inflammatory bowel disease (IBD) and characterized by fibrosing inflammatory destruction of biliary ducts. The pathogenesis of PSC remains unknown, but immunological, bacteria], viral, and toxic factors play a role in a genetically susceptible host. We hypothesized that CC-type chemokine receptor 5 (CCR5) would be ail interesting candidate gene for susceptibility to PSC from its chromosomal location within the IBD Susceptibility locus on 3p21, as well as from a functional perspective. We therefore investigated the role of the functional 32-bp deletion in this gene (CCR5-Delta 32) with regard to susceptibility to PSC. 
Methods: A total of 110 patients with PSC, 56 with concomitant IBD (23 with Crohn's disease, 28 with ulcerative colitis, 5 with indeterminate colitis), were collected. All of the subjects were genotyped for CCR5-Delta 32 with polymerase chain reaction amplification, followed by detection on ethidium bromide-stained agarose gel. Genotypes and allele frequencies were compared with a cohort of IBD patients without PSC (n = 400) and healthy control Subjects (n = 362). 
Results: The frequency of the CCR5-Delta 32 mutation in PSC (6.8\%) was significantly lower compared with IBD (12.6\%; P = 0.016) and healthy control subjects (12.2\%, P = 0.026), suggesting a protective effect of this mutation on PSC. None of the PSC patients with severe disease necessitating liver transplantation (it = 17) carried CCR5-Delta 32. 
Conclusions: Because an intact CCR5 receptor is needed for internalization of specific pathogens and homing of memory T lymphocytes to the liver, we hypothesize that a deficient expression of this receptor resulting from the CCR5-Delta 32 variant may protect against PSC.},
  author       = {Henckaerts, L and Fevery, J and Van Steenbergen, W and Werslype, C and Yap, P and Nevens, F and Roskams, T and Libbrecht, Louis and Rutgeerts, P and Vermeire, S},
  issn         = {1078-0998},
  journal      = {INFLAMMATORY BOWEL DISEASES},
  language     = {eng},
  number       = {4},
  pages        = {272--277},
  title        = {CC-type chemokine receptor 5-Delta 32 mutation protects against primary sclerosing cholangitis},
  url          = {http://dx.doi.org/10.1097/01.MIB.0000209790.21737.28},
  volume       = {12},
  year         = {2006},
}

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