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Title: POGLUT1, the putative effector gene driven by rs2293370 in primary biliary cholangitis susceptibility locus chromosome 3q13.33
Authors: Hitomi, Yuki
Ueno, Kazuko
Kawai, Yosuke
Nishida, Nao
Kojima, Kaname
Kawashima, Minae
Aiba, Yoshihiro
Nakamura, Hitomi
Kouno, Hiroshi
Kouno, Hirotaka
Ohta, Hajime
Sugi, Kazuhiro
Nikami, Toshiki
Yamashita, Tsutomu
Katsushima, Shinji
Komeda, Toshiki
Ario, Keisuke
Naganuma, Atsushi
Shimada, Masaaki
Hirashima, Noboru
Yoshizawa, Kaname
Makita, Fujio
Furuta, Kiyoshi
Kikuchi, Masahiro
Naeshiro, Noriaki
Takahashi, Hironao
Mano, Yutaka
Yamashita, Haruhiro
Matsushita, Kouki
Tsunematsu, Seiji
Yabuuchi, Iwao
Nishimura, Hideo
Shimada, Yusuke
Yamauchi, Kazuhiko
Komatsu, Tatsuji
Sugimoto, Rie
Sakai, Hironori
Mita, Eiji
Koda, Masaharu
Nakamura, Yoko
Kamitsukasa, Hiroshi
Sato, Takeaki
Nakamuta, Makoto
Masaki, Naohiko
Takikawa, Hajime
Tanaka, Atsushi
Ohira, Hiromasa
Zeniya, Mikio
Abe, Masanori
Kaneko, Shuichi
Honda, Masao
Arai, Kuniaki
Arinaga-Hino, Teruko
Hashimoto, Etsuko
Taniai, Makiko
Umemura, Takeji
Joshita, Satoru
Nakao, Kazuhiko
Ichikawa, Tatsuki
Shibata, Hidetaka
Takaki, Akinobu
Yamagiwa, Satoshi
Seike, Masataka
Sakisaka, Shotaro
Takeyama, Yasuaki
Harada, Masaru
Senju, Michio
Yokosuka, Osamu
Kanda, Tatsuo
Ueno, Yoshiyuki
Ebinuma, Hirotoshi
Himoto, Takashi
Murata, Kazumoto
Shimoda, Shinji
Nagaoka, Shinya
Abiru, Seigo
Komori, Atsumasa
Migita, Kiyoshi
Ito, Masahiro
Yatsuhashi, Hiroshi
Maehara, Yoshihiko
Uemoto, Shinji  kyouindb  KAKEN_id
Kokudo, Norihiro
Nagasaki, Masao  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-4292-8785 (unconfirmed)
Tokunaga, Katsushi
Nakamura, Minoru
Author's alias: 上本, 伸二
Issue Date: 14-Jan-2019
Publisher: Springer Nature
Journal title: Scientific reports
Volume: 9
Thesis number: 102
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.
Rights: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
URI: http://hdl.handle.net/2433/243759
DOI(Published Version): 10.1038/s41598-018-36490-1
PubMed ID: 30643196
Appears in Collections:Journal Articles

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