| 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 |
|