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J Hepatol. 1998 May;28(5):820-3.

No evidence for involvement of the interleukin-10 -592 promoter polymorphism in genetic susceptibility to primary biliary cirrhosis.

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  • 1Center for Liver Research, University of Newcastle, Newcastle-upon-Tyne, UK.

Abstract

BACKGROUND/AIMS:

Primary biliary cirrhosis is a chronic cholestatic liver disease with an autoimmune aetiology. Family studies, which have shown a significantly increased incidence of primary biliary cirrhosis in the close relatives of patients, suggest that genetic factors play a significant role in determining disease susceptibility. Several studies have previously identified loci which appear to play a role in determining this susceptibility, including the MHC class II allele HLA DR8, and the class III encoded C4A null allele (C4AQ0). Here, we have studied another candidate susceptibility locus in primary biliary cirrhosis, an apparently functional biallelic polymorphism at position -592 in the promoter region of the gene encoding the immuno-modulatory cytokine interleukin-10. Interleukin-10 plays an important role in the functional control, in vivo, of autoreactive Th-1 type CD4+ T-cells, with experimental manipulation of interleukin-10 leading to significant modulation of disease development in animal models of autoimmunity.

METHODS:

Interleukin-10 -592 genotypes were studied by polymerase chain reaction in 171 well-characterised, histologically-staged, primary biliary cirrhosis patients and 141 locally matched controls.

RESULTS:

Of 171 primary biliary cirrhosis patients, 99 were homozygous for the commoner allele (C/C), 68/171 (40%) were heterozygotes (A/C), whilst 4/171 (2%) were homozygous for the rarer allele (A/A). These genotype frequencies were not significantly different from those seen in controls (p=0.49, odds ratio 1.2 [0.8-1.91).

CONCLUSIONS:

These findings, in the first study of IL-10 as a candidate locus in a human autoimmune disease, suggest that IL-10 -592 is not a susceptibility locus in primary biliary cirrhosis.

PMID:
9625317
[PubMed - indexed for MEDLINE]
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