PMID- 30854688
OWN - NLM
STAT- MEDLINE
DCOM- 20200622
LR  - 20231213
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 70
IP  - 1
DP  - 2019 Jul
TI  - Genome-wide Association Studies of Specific Antinuclear Autoantibody 
      Subphenotypes in Primary Biliary Cholangitis.
PG  - 294-307
LID - 10.1002/hep.30604 [doi]
AB  - Anti-nuclear antibodies to speckled 100 kDa (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-wide association analysis of 930 PBC cases based on their 
      autoantibody status, followed by a replication study in 1,252 PBC cases. We 
      confirmed single-nucleotide polymorphisms rs492899 (P = 3.27 x 10(-22) ; odds 
      ratio [OR], 2.90; 95% confidence interval [CI], 2.34-3.66) and rs1794280 
      (P = 5.78 x 10(-28) ; OR, 3.89; 95% CI, 3.05-4.96) 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-sp100-positive versus 711 negative cases) using a Han Chinese MHC 
      reference database. Conditional analysis identified that HLA-DRbeta1-Asn77/Arg74, 
      DRbeta1-Ser37, and DPbeta1-Lys65 were major determinants for sp100 production. For the 
      classical HLA alleles, the strongest association was with DRB1*03:01 
      (P = 1.51 x 10(-9) ; OR, 2.97; 95% CI, 2.06-4.29). Regression analysis with 
      classical HLA alleles identified DRB1*03:01, DRB1*15:01, DRB1*01, and DPB1*03:01 
      alleles can explain most of the HLA association with sp100 autoantibody. 
      Conclusion: 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.
CI  - (c) 2019 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of 
      American Association for the Study of Liver Diseases.
FAU - Wang, Chan
AU  - Wang C
AUID- ORCID: 0000-0002-6198-773X
AD  - Key Laboratory of Developmental Genes and Human Diseases, Institute of Life 
      Sciences, Southeast University, Nanjing, Jiangsu, China.
FAU - Zheng, Xiaodong
AU  - Zheng X
AD  - 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.
FAU - Jiang, Peng
AU  - Jiang P
AD  - Key Laboratory of Developmental Genes and Human Diseases, Institute of Life 
      Sciences, Southeast University, Nanjing, Jiangsu, China.
FAU - Tang, Ruqi
AU  - Tang R
AD  - Department of Gastroenterology and Hepatology, Shanghai Institute of Digestive 
      Diseases, Shanghai Jiao Tong University School of Medicine Affiliated Renji 
      Hospital, Shanghai, China.
FAU - Gong, Yuhua
AU  - Gong Y
AD  - Department of Laboratory Medicine, The Third People's Hospital of Zhenjiang, 
      Zhenjiang, Jiangsu, China.
FAU - Dai, Yaping
AU  - Dai Y
AD  - Department of Laboratory Medicine, The Fifth People's Hospital of Wuxi, Wuxi, 
      Jiangsu, China.
FAU - Wang, Lan
AU  - Wang L
AD  - Department of Laboratory Medicine, The 81st Hospital of PLA, Nanjing, Jiangsu, 
      China.
FAU - Xu, Ping
AU  - Xu P
AD  - Department of Laboratory Medicine, The Fifth People's Hospital of Suzhou, Soochow 
      University, Suzhou, Jiangsu, China.
FAU - Sun, Wenjuan
AU  - Sun W
AD  - Key Laboratory of Developmental Genes and Human Diseases, Institute of Life 
      Sciences, Southeast University, Nanjing, Jiangsu, China.
FAU - Wang, Lu
AU  - Wang L
AD  - Key Laboratory of Developmental Genes and Human Diseases, Institute of Life 
      Sciences, Southeast University, Nanjing, Jiangsu, China.
FAU - Han, Chongxu
AU  - Han C
AD  - Department of Laboratory Medicine, Subei People's Hospital, Clinical Medical 
      College, Yangzhou University, Yangzhou, Jiangsu, China.
FAU - Jiang, Yuzhang
AU  - Jiang Y
AD  - Department of Laboratory Medicine, Huai'an First People's Hospital, Nanjing 
      Medical University, Huai'an, Jiangsu, China.
FAU - Wei, Yiran
AU  - Wei Y
AD  - Department of Gastroenterology and Hepatology, Shanghai Institute of Digestive 
      Diseases, Shanghai Jiao Tong University School of Medicine Affiliated Renji 
      Hospital, Shanghai, China.
FAU - Zhang, Kui
AU  - Zhang K
AD  - Department of Laboratory Medicine, Nanjing Drum Tower Hospital, The Affiliated 
      Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
FAU - Wu, Jian
AU  - Wu J
AD  - Department of Rheumatology, First Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu, China.
FAU - Shao, Youlin
AU  - Shao Y
AD  - Department of Hepatology, The Third People's Hospital of Changzhou, Changzhou, 
      Jiangsu, China.
FAU - Gao, Yueqiu
AU  - Gao Y
AD  - Department of Liver Diseases, Shuguang Hospital, Shanghai University of 
      Traditional Chinese Medicine, Shanghai, China.
FAU - Yu, Jianjiang
AU  - Yu J
AD  - Department of Laboratory Medicine, Jiangyin People's Hospital, Southeast 
      University, Jiangyin, Jiangsu, China.
FAU - Hu, Zhigang
AU  - Hu Z
AD  - Department of Laboratory Medicine, Affiliated Wuxi People's Hospital of Nanjing 
      Medical University, Wuxi, Jiangsu, China.
FAU - Zang, Zhidong
AU  - Zang Z
AD  - Department of Hepatology, The Second Hospital of Nanjing, Southeast University, 
      Nanjing, Jiangsu, China.
FAU - Zhao, Yi
AU  - Zhao Y
AD  - Department of Gastrointestinal Endoscopy, Eastern Hepatobiliary Surgery Hospital, 
      Shanghai, China.
FAU - Wu, Xudong
AU  - Wu X
AD  - Department of Gastroenterology, Yancheng First People's Hospital, Yancheng, 
      Jiangsu, China.
FAU - Dai, Na
AU  - Dai N
AD  - Department of Gastroenterology, Jiangsu University Affiliated Kunshan Hospital, 
      Kunshan, Jiangsu, China.
FAU - Liu, Lei
AU  - Liu L
AD  - Department of Gastroenterology, Yixing People's Hospital, Yixin, Jiangsu, China.
FAU - Nie, Jinshan
AU  - Nie J
AD  - Department of Gastroenterology, Taicang First People's Hospital, Soochow 
      University, Taicang, Jiangsu, China.
FAU - Jiang, Bo
AU  - Jiang B
AD  - Department of Hepatology, Jingjiang Second People's Hospital, Jingjiang, Jiangsu, 
      China.
FAU - Lin, Maosong
AU  - Lin M
AD  - Department of Gastroenterology, Taizhou People's Hospital, Taizhou, Jiangsu, 
      China.
FAU - Li, Li
AU  - Li L
AD  - Department of Laboratory Medicine, Zhongda Hospital, Southeast University, 
      Nanjing, Jiangsu, China.
FAU - Li, You
AU  - Li Y
AD  - Department of Gastroenterology and Hepatology, Shanghai Institute of Digestive 
      Diseases, Shanghai Jiao Tong University School of Medicine Affiliated Renji 
      Hospital, Shanghai, China.
FAU - Chen, Sufang
AU  - Chen S
AD  - Department of Laboratory Medicine, The Fifth People's Hospital of Suzhou, Soochow 
      University, Suzhou, Jiangsu, China.
FAU - Shu, Lixin
AU  - Shu L
AD  - Key Laboratory of Developmental Genes and Human Diseases, Institute of Life 
      Sciences, Southeast University, Nanjing, Jiangsu, China.
FAU - Qiu, Fang
AU  - Qiu F
AD  - Key Laboratory of Developmental Genes and Human Diseases, Institute of Life 
      Sciences, Southeast University, Nanjing, Jiangsu, China.
FAU - Wu, Qiuyuan
AU  - Wu Q
AD  - Key Laboratory of Developmental Genes and Human Diseases, Institute of Life 
      Sciences, Southeast University, Nanjing, Jiangsu, China.
FAU - Zhang, Mingming
AU  - Zhang M
AD  - Key Laboratory of Developmental Genes and Human Diseases, Institute of Life 
      Sciences, Southeast University, Nanjing, Jiangsu, China.
FAU - Chen, Ru
AU  - Chen R
AD  - Key Laboratory of Developmental Genes and Human Diseases, Institute of Life 
      Sciences, Southeast University, Nanjing, Jiangsu, China.
FAU - Jawed, Rohil
AU  - Jawed R
AD  - Key Laboratory of Developmental Genes and Human Diseases, Institute of Life 
      Sciences, Southeast University, Nanjing, Jiangsu, China.
FAU - Zhang, Yu
AU  - Zhang Y
AD  - Key Laboratory of Developmental Genes and Human Diseases, Institute of Life 
      Sciences, Southeast University, Nanjing, Jiangsu, China.
FAU - Shi, Xingjuan
AU  - Shi X
AD  - Key Laboratory of Developmental Genes and Human Diseases, Institute of Life 
      Sciences, Southeast University, Nanjing, Jiangsu, China.
FAU - Zhu, Zhen
AU  - Zhu Z
AD  - Department of Hepatology, The Third People's Hospital of Changzhou, Changzhou, 
      Jiangsu, China.
FAU - Pei, Hao
AU  - Pei H
AD  - Department of Laboratory Medicine, The Fifth People's Hospital of Wuxi, Wuxi, 
      Jiangsu, China.
FAU - Huang, Lihua
AU  - Huang L
AD  - Department of Laboratory Medicine, The Fifth People's Hospital of Wuxi, Wuxi, 
      Jiangsu, China.
FAU - Zhao, Weifeng
AU  - Zhao W
AD  - Department of Gastroenterology, First Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu, China.
FAU - Tian, Ye
AU  - Tian Y
AD  - Department of Radiology, The Second Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu, China.
FAU - Zhu, Xiang
AU  - Zhu X
AD  - Department of Laboratory Medicine, The Fifth People's Hospital of Suzhou, Soochow 
      University, Suzhou, Jiangsu, China.
FAU - Qiu, Hong
AU  - Qiu H
AD  - Department of Laboratory Medicine, The 81st Hospital of PLA, Nanjing, Jiangsu, 
      China.
FAU - Gershwin, M Eric
AU  - Gershwin ME
AD  - Division of Rheumatology, Allergy and Clinical Immunology, University of 
      California at Davis School of Medicine, Davis, CA.
FAU - Chen, Weichang
AU  - Chen W
AD  - Department of Gastroenterology, First Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu, China.
FAU - Seldin, Michael F
AU  - Seldin MF
AD  - Department of Biochemistry and Molecular Medicine, University of California at 
      Davis School of Medicine, Davis, CA.
FAU - Liu, Xiangdong
AU  - Liu X
AD  - Key Laboratory of Developmental Genes and Human Diseases, Institute of Life 
      Sciences, Southeast University, Nanjing, Jiangsu, China.
FAU - Sun, Liangdan
AU  - Sun L
AD  - 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.
FAU - Ma, Xiong
AU  - Ma X
AD  - Department of Gastroenterology and Hepatology, Shanghai Institute of Digestive 
      Diseases, Shanghai Jiao Tong University School of Medicine Affiliated Renji 
      Hospital, Shanghai, China.
LA  - eng
GR  - 81570469/National Natural Science Foundation of China/International
GR  - 81620108002/National Natural Science Foundation of China/International
GR  - 81770381/National Natural Science Foundation of China/International
GR  - 81771732/National Natural Science Foundation of China/International
GR  - 81830016/National Natural Science Foundation of China/International
GR  - 81870397/National Natural Science Foundation of China/International
GR  - BE2017713/Government of Jiangsu Province/International
GR  - BL2018657/Government of Jiangsu Province/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190429
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (Antigens, Nuclear)
RN  - 0 (Autoantigens)
RN  - 135844-47-2 (SP100 protein, human)
SB  - IM
MH  - Aged
MH  - Antibodies, Antinuclear/*genetics
MH  - Antigens, Nuclear/*immunology
MH  - Autoantigens/*immunology
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Liver Cirrhosis, Biliary/*genetics/immunology
MH  - Male
MH  - Middle Aged
PMC - PMC6618054
EDAT- 2019/03/12 06:00
MHDA- 2020/06/23 06:00
PMCR- 2019/07/10
CRDT- 2019/03/12 06:00
PHST- 2018/10/29 00:00 [received]
PHST- 2019/03/03 00:00 [accepted]
PHST- 2019/03/12 06:00 [pubmed]
PHST- 2020/06/23 06:00 [medline]
PHST- 2019/03/12 06:00 [entrez]
PHST- 2019/07/10 00:00 [pmc-release]
AID - HEP30604 [pii]
AID - 10.1002/hep.30604 [doi]
PST - ppublish
SO  - Hepatology. 2019 Jul;70(1):294-307. doi: 10.1002/hep.30604. Epub 2019 Apr 29.