{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:52:33Z","timestamp":1790211153759,"version":"4.1.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T00:00:00Z","timestamp":1556496000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:p>Anti\u2010nuclear antibodies to speckled 100\u00a0kDa (sp100) and glycoprotein 210 (gp210) are specific serologic markers of primary biliary cholangitis (PBC) of uncertain\/controversial clinical or prognostic significance. To study the genetic determinants associated with sp100 and gp210 autoantibody subphenotypes, we performed a genome\u2010wide association analysis of 930 PBC cases based on their autoantibody status, followed by a replication study in 1,252 PBC cases. We confirmed single\u2010nucleotide polymorphisms rs492899 (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a03.27\u00a0\u00d7\u00a010<jats:sup>\u221222<\/jats:sup>; odds ratio [OR], 2.90; 95% confidence interval [CI], 2.34\u20103.66) and rs1794280 (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a05.78\u00a0\u00d7\u00a010<jats:sup>\u221228<\/jats:sup>; OR, 3.89; 95% CI, 3.05\u20104.96) in the human major histocompatibility complex (MHC) region associated with the sp100 autoantibody. However, no genetic variant was identified as being associated with the gp210 autoantibody. To further define specific classical human leukocyte antigen (HLA) alleles or amino acids associated with the sp100 autoantibody, we imputed 922 PBC cases (211 anti\u2010sp100\u2010positive versus 711 negative cases) using a Han Chinese MHC reference database. Conditional analysis identified that HLA\u2010DR\u03b21\u2010Asn77\/Arg74, DR\u03b21\u2010Ser37, and DP\u03b21\u2010Lys65 were major determinants for sp100 production. For the classical HLA alleles, the strongest association was with <jats:italic toggle=\"yes\">DRB1*03:01<\/jats:italic> (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a01.51\u00a0\u00d7\u00a010<jats:sup>\u22129<\/jats:sup>; OR, 2.97; 95% CI, 2.06\u20104.29). Regression analysis with classical HLA alleles identified <jats:italic toggle=\"yes\">DRB1*03:01<\/jats:italic>, <jats:italic toggle=\"yes\">DRB1*15:01<\/jats:italic>, <jats:italic toggle=\"yes\">DRB1*01<\/jats:italic>, and <jats:italic toggle=\"yes\">DPB1*03:01<\/jats:italic> alleles can explain most of the HLA association with sp100 autoantibody. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: This study indicated significant genetic predisposition to the sp100 autoantibody, but not the gp210 autoantibody, subphenotype in PBC patients. Additional studies will be necessary to determine if these findings have clinical significance to PBC pathogenesis and\/or therapeutics.<\/jats:p>","DOI":"10.1002\/hep.30604","type":"journal-article","created":{"date-parts":[[2019,3,11]],"date-time":"2019-03-11T06:50:06Z","timestamp":1552287006000},"page":"294-307","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":36,"title":["Genome\u2010wide Association Studies of Specific Antinuclear Autoantibody Subphenotypes in Primary Biliary Cholangitis"],"prefix":"10.1097","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6198-773X","authenticated-orcid":false,"given":"Chan","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences,Southeast University,Nanjing,Jiangsu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Dermatology,The First Affiliated Hospital of Anhui Medical University, and Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China & Key Laboratory of Major Autoimmune Diseases, Anhui Province,Hefei,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences,Southeast University,Nanjing,Jiangsu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruqi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Shanghai Institute of Digestive Diseases, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine,The Third People's Hospital of Zhenjiang,Zhenjiang,Jiangsu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine,The Fifth People's Hospital of Wuxi,Wuxi,Jiangsu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine,The 81st Hospital of PLA,Nanjing,Jiangsu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine,The Fifth People's Hospital of Suzhou, Soochow University,Suzhou,Jiangsu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences,Southeast University,Nanjing,Jiangsu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences,Southeast University,Nanjing,Jiangsu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongxu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine,Subei People's Hospital, Clinical Medical College, Yangzhou University,Yangzhou,Jiangsu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine,Huai'an First People's Hospital, Nanjing Medical University,Huai'an,Jiangsu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Shanghai Institute of Digestive Diseases, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine,Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School,Nanjing,Jiangsu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology,First Affiliated Hospital of Soochow University,Suzhou,Jiangsu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youlin","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Hepatology,The Third People's Hospital of Changzhou,Changzhou,Jiangsu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueqiu","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Liver Diseases,Shuguang Hospital, Shanghai University of Traditional Chinese Medicine,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine,Jiangyin People's Hospital, Southeast University,Jiangyin,Jiangsu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine,Affiliated Wuxi People's Hospital of Nanjing Medical 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