Journal of Hepatology 2000; 32: 882-886 Printed in Denmark AN rights reserved Munksgaard~ Copenhagen Cop.vrighr 0 European Association for the Stud], of the Liver 2000 zyxwvutsr Journal of Hepatology ISSN 0168-8278 The interleukin-1 and interleukin-10 gene polymorphismsin primary sclerosing cholangitis: no associations with disease susceptibility/resistance Peter T. Donaldson’, Suzanne Norris2, Patrizia K. Constantini*, Will Bernal*, Phillip Harrison2 and Roger Williams3 ‘Centre for Liver Research, School of Clinical Medical Sciences, The Medical School, University of Newcastle, Newcastle upon Sne. ‘Institute of Liver Studies, King’s College Hospital and 31nstitute of Hepatology, Royal Free & University College Medical School. London. UK Background/Aims: Although primary sclerosing chol- angitis is believed to be an autoimmune disorder, no tissue-specific auto-antibodies have yet been iden- tified, and the strongest support for an autoimmune aetiology comes from HLA-association studies. Three different HLA haplotypes are associated with suscep- tibility to the disease and one with protection from it. These HLA haplotypes, however, do not account for all of the disease risk and genes outside the HLA re- gion may also have a role in disease pathogenesis. The aim of this study was to investigate, for the first time, polymorphic genes/sites within the interleukin-1 and interleukin-10 genes in a large well-characterised group of patients. Metltods: Ninety-six patients and 96 control subjects were studied. A single base-exchange polymorphism at position +3953 in the first exon of the IL-IB gene, a penta-allelic repeat sequence in the IL-l receptor antagonist gene (IL-IRN) and three single base-ex- change polymorphisms at positions -592, -819 and p” IMARY SCLEROSING cholangitis (PSC) is character- ised by the obliterative inflammation of the extra- and intra-hepatic bile ducts and is associated with in- flammatory bowel disease, mostly ulcerative colitis (UC) in 70 to 100% of cases. Although PSC is believed to be an autoimmune disease, no tissue-specific auto- antibodies have yet been identified and the aetiology of Received 12 August, revised 20 October; accepted 3 November 1999 Correspondence: Peter T. Donaldson, Centre for Liver Re- search, School of Clinical Medical Sciences, The Medical School, University of Newcastle, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. Tel: 44 191 222 8688. Fax: 44 191 222 0723. e-mail: I?T.Donaldson@ncl.ac.uk -1082 in the IL-10 gene promoter were determined by standard PCR-based techniques. Results: Overall, there was no significant difference in the distribution of any of the IL-IB, IL-IRN or IL-10 alleles or genes sequences comparing patients and controls. In addition, there was no difference when the patients were stratified for the presence and absence of the HLA DRBl”O301 (DR3) allele or con- current inflammatory bowel disease. Conclusion: Neither the IL-1B +3953, IL-1RN microsatellites polymorphisms on chromosome 2q13 nor the IL-10 -592, -819, -1082 promoter gene polymorphisms on chromosome lq31-32 are associ- ated with susceptibility or resistance to primary sclerosing cholangitis. Key words: Autoimmunity; HLA DRBl*0301; ZL- 1B; IL-IRN; IL-10 promoter; Inflammatory bowel disease; Interleukin-1; Interleukin-10; Primary sclerosing cholangitis. the disease remains unknown. The only candidate auto-antibody, perinuclear anti-neutrophil cytoplasmic antibody (pANCA), which is present in up to 80% of PSC patients, is also found in autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and ulcerative colitis (UC) (1). Studies of the HLA genotypes of PSC patients suggest that there may be a strong genetic component to this disease. Three HLA haplotypes are associated with susceptibility (i.e. increased risk): 1) A1-B8-TNF2-DRB3*01#1-DRB1*0301-DQB1*0201, 2) DRBl*I301-DQAI *0103-DQBl*O603, 3) DRBl*1501-DQAI *0102-DQBl”O602, and a fourth haplotype: DRB4*0103-DRBI *0401-DQBI *0302 may be associated with resistance (i.e. reduced risk) (2-8). Though there is general agreement about the basic 882