POGLUT1, the putative effector gene driven by rs2293370 in primary biliary cholangitis susceptibility locus chromosome 3q13.33 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-01-14

AUTHORS

Yuki Hitomi, Kazuko Ueno, Yosuke Kawai, Nao Nishida, Kaname Kojima, Minae Kawashima, Yoshihiro Aiba, Hitomi Nakamura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ohta, Kazuhiro Sugi, Toshiki Nikami, Tsutomu Yamashita, Shinji Katsushima, Toshiki Komeda, Keisuke Ario, Atsushi Naganuma, Masaaki Shimada, Noboru Hirashima, Kaname Yoshizawa, Fujio Makita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Haruhiro Yamashita, Kouki Matsushita, Seiji Tsunematsu, Iwao Yabuuchi, Hideo Nishimura, Yusuke Shimada, Kazuhiko Yamauchi, Tatsuji Komatsu, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Yoko Nakamura, Hiroshi Kamitsukasa, Takeaki Sato, Makoto Nakamuta, Naohiko Masaki, Hajime Takikawa, Atsushi Tanaka, Hiromasa Ohira, Mikio Zeniya, Masanori Abe, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Akinobu Takaki, Satoshi Yamagiwa, Masataka Seike, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo Kanda, Yoshiyuki Ueno, Hirotoshi Ebinuma, Takashi Himoto, Kazumoto Murata, Shinji Shimoda, Shinya Nagaoka, Seigo Abiru, Atsumasa Komori, Kiyoshi Migita, Masahiro Ito, Hiroshi Yatsuhashi, Yoshihiko Maehara, Shinji Uemoto, Norihiro Kokudo, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura

ABSTRACT

Primary biliary cholangitis (PBC) is a chronic and cholestatic autoimmune liver disease caused by the destruction of intrahepatic small bile ducts. Our previous genome-wide association study (GWAS) identified six susceptibility loci for PBC. Here, in order to further elucidate the genetic architecture of PBC, a GWAS was performed on an additional independent sample set, then a genome-wide meta-analysis with our previous GWAS was performed based on a whole-genome single nucleotide polymorphism (SNP) imputation analysis of a total of 4,045 Japanese individuals (2,060 cases and 1,985 healthy controls). A susceptibility locus on chromosome 3q13.33 (including ARHGAP31, TMEM39A, POGLUT1, TIMMDC1, and CD80) was previously identified both in the European and Chinese populations and was replicated in the Japanese population (OR = 0.7241, P = 3.5 × 10-9). Subsequent in silico and in vitro functional analyses identified rs2293370, previously reported as the top-hit SNP in this locus in the European population, as the primary functional SNP. Moreover, e-QTL analysis indicated that the effector gene of rs2293370 was Protein O-Glucosyltransferase 1 (POGLUT1) (P = 3.4 × 10-8). This is the first study to demonstrate that POGLUT1 and not CD80 is the effector gene regulated by the primary functional SNP rs2293370, and that increased expression of POGLUT1 might be involved in the pathogenesis of PBC. More... »

PAGES

102

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  • Journal

    TITLE

    Scientific Reports

    ISSUE

    1

    VOLUME

    9

    Author Affiliations

  • Department of Human Genetics, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
  • Graduate School of Medicine, Tohoku University, Sendai, Japan
  • The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan
  • Japan Science and Technology Agency (JST), Tokyo, Japan
  • Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Omura, Japan
  • Headquarters of PBC Research in NHO Study Group for Liver Disease in Japan (NHOSLJ), Clinical Research Center, NHO Nagasaki Medical Center, Omura, Japan
  • Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
  • Department of Gastroenterology and Rheumatic Diseases, Fukushima Medical University of Medicine, Fukushima, Japan
  • Department of Gastroenterology and Hepatology, Tokyo Jikei University School of Medicine, Tokyo, Japan
  • Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan
  • Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
  • Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
  • Department of Medicine and Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan
  • Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan
  • Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  • Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • Faculty of Medicine, Oita University, Oita, Japan
  • Department of Gastroenterology and Medicine, Fukuoka University School of Medicine, Fukuoka, Japan
  • The Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
  • Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
  • Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
  • Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio Graduate School of Medicine, Tokyo, Japan
  • Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Kagawa, Japan
  • Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
  • Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
  • Department of Surgery and Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
  • Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • National Center for Global Health and Medicine, Tokyo, Japan
  • Graduate School of Information Sciences, Tohoku University, Sendai, Japan
  • Headquaters of PBC-GWAS study group in Japan, Clinical Research Center, NHO Nagasaki Medical Center, Omura, Japan
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-018-36490-1

    DOI

    http://dx.doi.org/10.1038/s41598-018-36490-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111273932

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30643196


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