{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T01:26:08Z","timestamp":1784769968679,"version":"3.55.0"},"reference-count":50,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"accepted":{"date-parts":[[2000,9,25]]},"published-print":{"date-parts":[[2001,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND AND AIMS<\/jats:title>\n                    <jats:p>Twin and family studies suggest that there is a genetic component to primary biliary cirrhosis (PBC) but the genetic associations which have been described are weak with marked variations between centres. PBC is heterogeneous and genetic associations with disease progression may be obscured when the PBC population is analysed only as a whole and not subdivided.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec sec-type=\"methods\">\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We have investigated two candidate gene loci in 164 well characterised patients, 88 (54%) of whom had advanced disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      There was an increased frequency of the\n                      <jats:italic>HLA<\/jats:italic>\n                      <jats:italic>DRB1*0801-DQA1*0401-DQB1*0402<\/jats:italic>\n                      haplotype in patients who had progressed to late stage disease (23%\n                      <jats:italic>v<\/jats:italic>\n                      2% of controls; p=0000044; odds ratio (OR) 15.5, 95% confidence interval (CI) 3.52\u201368.4) but not in those with early stage disease (4%\n                      <jats:italic>v<\/jats:italic>\n                      2%). Patients had a higher frequency of the\n                      <jats:italic>IL-1B*1,1<\/jats:italic>\n                      genotype and lower frequencies of the\n                      <jats:italic>IL-1B*1,2<\/jats:italic>\n                      and\n                      <jats:italic>*2,2<\/jats:italic>\n                      genotypes (p=0.00078; OR 2.37, 95% CI 1.38\u20134.06), and higher frequency of the\n                      <jats:italic>IL-1RN*1,1<\/jats:italic>\n                      genotype and lower frequency of the\n                      <jats:italic>IL-1RN*1,2<\/jats:italic>\n                      genotype (p=0.0011; OR 2.28, 95% CI 1.34\u20133.89). The difference in the\n                      <jats:italic>IL-1B*1,1<\/jats:italic>\n                      genotype distribution was most marked in patients with early stage disease (77%\n                      <jats:italic>v<\/jats:italic>\n                      43% of controls; p=0.000003; OR 4.8, 95% CI 2.31\u201310) but the\n                      <jats:italic>IL-1RN<\/jats:italic>\n                      genotype distribution was similar in patients with early and late stage disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>\n                      These data indicate a complex relationship between immunoregulatory genes and PBC. While the\n                      <jats:italic>IL-1<\/jats:italic>\n                      genes are markers of both disease susceptibility and progression, HLA genes appear to be principally associated with disease progression.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gut.48.3.397","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T06:37:59Z","timestamp":1027751879000},"page":"397-402","source":"Crossref","is-referenced-by-count":109,"title":["HLA and interleukin 1 gene polymorphisms in primary biliary cirrhosis: associations with disease progression and disease susceptibility"],"prefix":"10.1136","volume":"48","author":[{"given":"P","family":"Donaldson","sequence":"first","affiliation":[{"name":"Centre for Liver Research, University of Newcastle, Newcastle-upon-Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Centre for Liver Research, University of Newcastle, Newcastle-upon-Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Craggs","sequence":"additional","affiliation":[{"name":"Centre for Liver Research, University of Newcastle, Newcastle-upon-Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Craig","sequence":"additional","affiliation":[{"name":"Centre for Liver Research, University of Newcastle, Newcastle-upon-Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"James","sequence":"additional","affiliation":[{"name":"Centre for Liver Research, University of Newcastle, Newcastle-upon-Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Jones","sequence":"additional","affiliation":[{"name":"Centre for Liver Research, University of Newcastle, Newcastle-upon-Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2001,3,1]]},"reference":[{"key":"2025121307323773000_48.3.397.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199611213352107"},{"key":"2025121307323773000_48.3.397.2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510300213"},{"key":"2025121307323773000_48.3.397.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(99)80097-X"},{"key":"2025121307323773000_48.3.397.4","doi-asserted-by":"crossref","first-page":"7.1","DOI":"10.1016\/S1089-3261(05)70007-6","article-title":"Primary biliary cirrhosis:clinical and associated autoimmune features and natural history.","volume":"2","author":"Jones","year":"1998","journal-title":"Clin Liver Dis"},{"key":"2025121307323773000_48.3.397.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)04410-8"},{"key":"2025121307323773000_48.3.397.6","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510230108"},{"key":"2025121307323773000_48.3.397.7","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1056\/NEJM197309272891306","article-title":"The presentation and diagnosis of 100 patients with primary biliary cirrhosis.","volume":"289","author":"Sherlock","year":"1973","journal-title":"N Engl J Med"},{"key":"2025121307323773000_48.3.397.8","doi-asserted-by":"publisher","DOI":"10.1136\/gut.14.3.213"},{"key":"2025121307323773000_48.3.397.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(05)80137-0"},{"key":"2025121307323773000_48.3.397.10","doi-asserted-by":"publisher","DOI":"10.1136\/gut.36.4.615"},{"key":"2025121307323773000_48.3.397.11","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840070516"},{"key":"2025121307323773000_48.3.397.12","unstructured":"Donaldson PT Manns MP (1999) Immunogenetics of liver disease. in Oxford textbook of clinical hepatology. eds Bircher J Benhamou J-P McIntyre N (Oxford University Press, Oxford), pp 173\u2013188."},{"key":"2025121307323773000_48.3.397.13","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/j.1399-0039.1987.tb01566.x","article-title":"R. 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