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| dc.creator | Mitchell, S .A. | |
| dc.creator | Grove, J. | |
| dc.creator | Spurkland, A. | |
| dc.creator | Boberg, Kirsten M. | |
| dc.creator | Fleming, K. A. | |
| dc.creator | Day, Christopher P. | |
| dc.creator | Schrumpf, E. | |
| dc.creator | Chapman, Roger W. | |
| dc.creator | Parés Darnaculleta, Albert | |
| dc.creator | Caballeria Rovira, Joan | |
| dc.creator | Rodés, J. | |
| dc.date | 2011-07-07T12:30:22Z | |
| dc.date | 2011-07-07T12:30:22Z | |
| dc.date | 2001 | |
| dc.date.accessioned | 2024-12-16T10:27:14Z | |
| dc.date.available | 2024-12-16T10:27:14Z | |
| dc.identifier | 0017-5749 | |
| dc.identifier | http://hdl.handle.net/2445/18651 | |
| dc.identifier | 583543 | |
| dc.identifier | 11454808 | |
| dc.identifier.uri | http://fima-docencia.ub.edu:8080/xmlui/handle/123456789/22123 | |
| dc.description | BACKGROUND AND AIMS Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology. Abnormalities in immune regulation and genetic associations suggest that PSC is an immune mediated disease. Several polymorphisms within the tumour necrosis factor α (TNF-α) and interleukin 10 (IL-10) promoter genes have been described which influence expression of these cytokines. This study examines the possible association between polymorphisms at the −308 and −627 positions in the TNF-α and IL-10 promoter genes, respectively, and susceptibility to PSC. METHODS TNF-α −308 genotypes were studied by polymerase chain reaction (PCR) in 160 PSC patients from Norway and the UK compared with 145 ethnically matched controls. IL-10 −627 genotypes were studied by PCR in 90 PSC patients compared with 84 ethnically matched controls. RESULTS A total of 16% of Norwegian PSC patients and 12% of British PSC patients were homozygous for the TNF2 allele compared with 3% and 6% of respective controls. The TNF2 allele was present in 60% of PSC patients versus 30% of controls (ORcombined data=3.2 (95% confidence intervals (CI) 1.8–4.5); pcorr=10−5). The association between the TNF2 allele and susceptibility to PSC was independent of the presence of concurrent inflammatory bowel disease (IBD) in the PSC patients; 61% of PSC patients without IBD had TNF2 compared with 30% of controls (ORcombined data=3.2 (95% CI 1.2–9.0); pcorr=0.006 ). There was no difference in the −627 IL-10 polymorphism distributions between patients and controls in either population. The increase in TNF2 allele in PSC patients only occurs in the presence of DRB1*0301 (DR3) and B8. In the combined population data, DRB1*0301 showed a stronger association with susceptibility to PSC than both the TNF2 and B8 alleles (ORcombined data=3.8, pcorr=10−6 v ORcombined data=3.2, pcorr=10−5 vORcombined data =3.41, pcorr=10−4, respectively). CONCLUSIONS This study identified a significant association between possession of the TNF2 allele, a G→A substitution at position −308 in the TNF-α promoter, and susceptibility to PSC. This association was secondary to the association of PSC with the A1-B8-DRB1*0301-DQA1*0501-DQB1*0201 haplotype. No association was found between the IL-10 −627 promoter polymorphism and PSC. | |
| dc.format | 7 p. | |
| dc.format | application/pdf | |
| dc.language | eng | |
| dc.publisher | BMJ Group | |
| dc.relation | Reproducció digital del document publicat a: http://dx.doi.org/10.1136/gut.49.2.288 | |
| dc.relation | Gut, 2001, vol. 49, núm. 2, p. 288-294 | |
| dc.relation | http://dx.doi.org/10.1136/gut.49.2.288 | |
| dc.rights | (c) BMJ Publishing Group Ltd and British Society of Gastroenterology, 2001 | |
| dc.rights | info:eu-repo/semantics/openAccess | |
| dc.source | Articles publicats en revistes (Medicina) | |
| dc.subject | Genètica mèdica | |
| dc.subject | Colèdoc | |
| dc.subject | Cèl·lules canceroses | |
| dc.subject | Necrosi | |
| dc.subject | Citoquines | |
| dc.subject | Medical genetics | |
| dc.subject | Coledocus | |
| dc.subject | Cancer cells | |
| dc.subject | Necrosis | |
| dc.subject | Cytokines | |
| dc.title | Association of the tumour necrosis factor alpha -308 but not the interleukin 10 -627 promoter polymorphism with genetic susceptibility to primary sclerosing cholangitis | |
| dc.type | info:eu-repo/semantics/article | |
| dc.type | info:eu-repo/semantics/publishedVersion |
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